MXPA00000859A

MXPA00000859A - Novel compound having effect of promoting neuron differentiation

Info

Publication number: MXPA00000859A
Application number: MXPA/A/2000/000859A
Authority: MX
Inventors: Seiichi Saito; Masashi Nagai; Tomio Morino; Tsugio Tomiyoshi; Takaaki Nishikiori; Atsushi Kuwahara; Takamichi Sato; Takashi Harada
Original assignee: Nippon Kayaku Kabushiki Kaisha
Priority date: 1997-07-25
Filing date: 2000-01-25
Publication date: 2001-12-04

Abstract

A novel cystacycline derivative which has an excellent effect of promoting the differentiation of neurons and is useful as a remedy for central nervous system disorders, a remedy for peripheral nerve disorders, etc.

Description

COMPOSITE NOVEDOSO THAT HAS THE EFFECT OF PROMOTION OF DIFERENTIATION OF NEURONS TECHNICAL FIELD The present invention relates to novel compounds that have a neuron differentiator promoting activity and the pharmaceutical use thereof.

ANTECEDENTS OF THE TECHNIQUE The neurotrophic factors are proteinaceous compounds that participate in the induction of differentiation of neurons and in the maintenance of the existence and survival of nerve cells. Nerve growth factors (hereinafter abbreviated frequently as NGF) are known to be representative of such compounds (Ann Neuro., 10, 499-503 (1981)). It is shown that NGF are deeply involved in the differentiation, maintenance of existence and repair of neurons in both the central and peripheral nervous systems. Damage to the nerves caused by aging, internal and external factors, often develop pathological symptoms. It has been found that such damages cause, in the central nervous system, Alzheimer's disease, dementia induced by cerebrovascular disorders, alterations of consciousness due to cerebral contusion, tremors or muscular rigidity due to Parkinson's disease, etc. It is also known that damage to the peripheral nervous system is induced by amyotrophic lateral sclerosis, spinal muscle atrophy, motor function disorders due to damage to the neuron accompanied by accidents, etc., and that neuropathies are induced by diabetes mellitus. , uremia, deficiency of vitamin Bl or B12, chronic liver disease, sarcoidosis, amyloidosis, hypothyroidism, cancer, angiopathy, symptoms of Sjögren, immunopathy accompanied by infections, hereditary disease, physical compression, medications (carcinostatic agents, tuberculostatic agents, antiepileptic agents, etc) or intoxication (arsenic, thallium, carbon disulphide, etc); in more detail, see RINSHO KENSA (Clinical Test), 40, 760-766 (1996). It has been recognized in the art that when a neuron suffers irreversible damage from these disorders, it is difficult to regenerate and repair damaged neurons. However, under the hypothesis that neuropathy can be treated if neurotrophic factors act on neurons, neurotrophic factors have been developed as anti-neuropathy drugs.

(Science, 264, 772-774 (1994)). For example, a clinical trial of NGF against Alzheimer's disease, neural damage or spinal cord damage is in progress.

NGFs are a series of proteins that have approximately a molecular weight of 50,000. For the treatment of neuropathy, a prolonged period of time is usually required. For these reasons, it is difficult to develop an efficient administration and a pharmaceutical formulation. Gene therapy, specifically the induction of the gene for NGF, is also another choice for treatment but its therapeutic effect is still unclear. It is known that when NGFs are not present, -PC 12 cells which are the established cell line cloned from rat adrenal pheochromocytoma pheochromocytoma-end cell proliferation and differentiate into neuron-like cells with neurites. This method allows to analyze an effective substance that has a promoter activity of neuron differentiation similar to NGF. For example, it has been found that in staurosporine antibiotic it has a PC12 cell differentiation promoting activity (SHINKEI KAGAKU, 26, 200-220 (1987)). Recently, a similar differentiation promoting activity has been observed in the active biological compound NK175203 (hereinafter referred to as cystacycline) which is produced from Streotomyces sp. NK175203 strain FERM BP-4372 (WO 95/31992). However, the toxicity and pharmacokinetics of staurosporine in vivo make its application as a medicine difficult. Therefore, it has been strongly desired to develop a low molecular weight compound that exhibits neuron differentiation promoting activity, is low in toxicity and is easily prepared synthetically.

DESCRIPTION OF THE INVENTION The present inventors have conducted extensive investigations with respect to the cystacycline derivatives and as a result, have found novel compounds represented by the general formulas [ÍA], [IB], [ÍC], [ID], [ÍE] and [1F] and pharmacologically acceptable salts thereof. Therefore, the present invention has been carried out. The present invention relates to the following compounds and compositions comprising the same. 1) A cyclopentanone derivative represented by the formula [ÍA]: wherein: Xs is O, S, SO, S02 or NH; YA is a linear or branched aliphatic hydrocarbon group having from 1 to 20 carbon atoms, which may be substituted or unsubstituted or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms. carbon; each of Z1A, Z2A and Z3A, which may be the same or different and independently represent carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived from the same, amino or a group derived therefrom, sulfonate or a derivative thereof, phosphate or a group derived therefrom, a monocyclic heteroaryl, a halogen or a hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon or an aromatic heterocyclic ring; and Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen, with the condition that when Z2A and Z3A are both hydrogen, Z1A is hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a monocyclic aromatic heterocyclic ring, a halogen or hydrogen, and YA is an aliphatic hydrocarbon group of linear or branched chain substituted or unsubstituted having from 1 to 6 carbon atoms; with the proviso that subsections (1) to (7) are excluded: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl, and Z3A is methoxycarbonyl, (2) when Z1A and Z2A is hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N u 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen; or a pharmacologically acceptable salt thereof; a 2,3-disubstituted cyclopentanone derivative of the formula [IB]: wherein: XB is 0, S, S0, S02 or NH; YB is: an unsubstituted or substituted straight or branched chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms, a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: minus one hydrogen is substituted with C0W1 (wherein W1 is an unsubstituted or substituted aromatic heterocyclic ring or a saturated heterocyclic ring) and at least one hydrogen may be further substituted with an amino derivative group; or at least one hydrogen is substituted with NHCOV1 (wherein VI is an alkyl having from 2 to 5 carbon atoms containing from 4 to 11 halogen atoms) and at least one hydrogen may also be substituted with carboxy or a group derived from it; or at least one hydrogen is substituted with a substituted or unsubstituted monocyclic aromatic heterocyclic ring and at least one hydrogen may be further substituted with amino or a group derived therefrom; or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms; ZB is carboxy or a group derived therefrom, sulfonate or a group derived therefrom, phosphate or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy, ORÍ (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NHC0R2 (wherein R2 is an unsubstituted or substituted alkyl having 1 to 4) carbon atoms), NHS02R2 '(where R2 'is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or phenyl), a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; or a pharmacologically acceptable salt thereof; a cyclopentanone derivative of formula [IC]: wherein: l ^ 10 a ring A has a double bond conjugated with oxo; Xc is O, S, SO, S02 or NH; Xc is a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or ring A monocyclic aromatic heterocyclic having from 3 to 6 carbon atoms; each of Zlc, Z2C and Z3C, which may be the same or different W and independently represent carboxy or a group derived therefrom, hydroxy or a group derived therefrom, 20 amino or a group derived therefrom, an unsubstituted alkyl or substituted or an alkenyl having from 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen atom or a hydrogen; with the proviso that when Xc is 0 or NH, Zlc and Z3C are not hydrogen and Z2C are not hydrogen or hydroxy or a group derived therefrom, or a pharmacologically acceptable salt thereof; 5 a ketone derivative of formula [ID]: wherein: AD is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms, an unsubstituted or substituted aromatic hydrocarbon, a heterocyclic ring or a saturated heterocyclic ring; BD is hydrogen or a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; or AD and BD combine together to form an unsubstituted or substituted cycloalkan-1-one ring having from 3 to 7 carbon atoms (except for 5 carbon atoms); XD is O, S, SO, S02 or NH; It is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms. carbon; ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived from the same or phosphate or a group derived therefrom, a heterocyclic ring # monocyclic aromatic, a halogen or hydrogen; with the proviso that, when AD and BD are combined together to form a cyclobutane ring, the following subparagraphs (1) to (4) are excluded: 15 (1) XD is O, YD is methyl, n-octyl or n hexadecyl and ZD is methoxycarbonyl; (2) XD is O, YD is benzyl and ZD is benzyloxymethyl; (3) XD is O, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and 20 (4) XD is O, YD trityl and ZD is trityloxymethyl or when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy; or a pharmacologically acceptable salt thereof; a compound of formula [ÍE]: or a pharmacologically acceptable salt thereof; or a β-disubstituted aminoketone derivative of the formula [1F]: wherein: AF is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms or an unsubstituted or substituted aromatic hydrocarbon ring, an aromatic heterocyclic ring or a saturated heterocyclic ring; BF is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms; or AF and BF combine together to form an unsubstituted or substituted cycloalkan-1-one ring having from 3 to 7 carbon atoms or to form a cycloalkan-1-one ring having from 3 to 7 carbon atoms and fuse with an aromatic hydrocarbon or an aromatic heterocyclic ring; each of XF and YF is an unsubstituted or substituted straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms or XF and YF are linked together directly or via a heteroatom to form an unsubstituted heterocyclic ring or replaced; ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived from the same, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen; with the proviso that when AF is an unsubstituted benzene ring we exclude those where BF is hydrogen, XF and YF are linked together directly to form a piperidine ring and ZF is carboxy; or a pharmacologically acceptable salt thereof. 2) A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: XA is S, O, S or SO; YA is a straight or branched chain aliphatic hydrocarbon group having from 1 to 20 carbon atoms (wherein at least one hydrogen atom is substituted with carboxy or a group derived therefrom or amino or a group derived therefrom); each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom , amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon or an aromatic heterocyclic ring; and Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen. 3) A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, according to item 2) described above, wherein: XA is S; YA is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein; at least one hydrogen atom is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms), C0W1 (wherein W1 is an unsubstituted heterocyclic ring) or substituted with carboxy or a group derived therefrom) or NR2R3 (wherein each of R2 and R3, which may be the same or different independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy, COOR4 (wherein R4 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6 which may independently be different or the same, represent hydrogen or a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms), cyano, hydroxy, 0R7 (wherein R7 is an unsubstituted or substituted alkyl) having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9 which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH 2 OR 10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an aci unsubstituted or substituted having 1 to 5 carbon atoms), chlorine, fluoro or hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon; and Z1A is carboxy, C00R4 (wherein R4 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6 which may be independently the same or different, represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9, which independently can be the same or different represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), chlorine, fl uoro or hydrogen. 4) A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, according to item 3) described above, wherein: XA is S; rmii-ffii'iii YA is a straight chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: at least two hydrogen atoms are substituted with any carboxy, C00R1 '(where R1' is an alkyl , an alkenyl or alkynyl having from 1 to 4 carbon atoms), C0W2 (wherein W2 is a saturated heterocyclic ring unsubstituted or substituted with C00R11 (wherein Rll is an alkyl having 1 to 4 carbon atoms) or NHC0R12 (wherein R12 is an alkyl having 1 to 4 carbon atoms), each of Z1A, Z2A and Z3A, which may be the same or different and independently represent carboxy, C00R4 '(wherein R4' is a alkyl having 1 to 4 carbon atoms), hydroxy, OCOR13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CHOR10 '(wherein RIO' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen; or Z2A and Z3A are combined bound to form a benzene ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms, an alkyloxy having 1 to 4 carbon atoms, nitro, trifluoromethyl or halogen; and Z1A is carboxy, C00R4 '(wherein R4' is an alkyl having 1 to 4 carbon atoms), hydroxy, OCOR13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CH2OR10 '( wherein RIO1 is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen. 5) A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, according to item 4) described above, wherein: XA is S; YA is a straight chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: a hydrogen is substituted with carboxy, methoxycarbonyl, COW3 (wherein W3 is a pyrrolidine, piperidine, azetidine, morpholine, or piperazine ring) which may be unsubstituted or substituted with methoxycarbonyl) and the other hydrogen is substituted with acetylamino; each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen; or Z2A and Z3A combine together to form an unsubstituted benzene ring; and Zl, is carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen. 6) A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, according to item 5) described above, wherein the cyclopentanone derivative is selected from the group consisting of: (I) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z1A and Z3A are hydrogen and Z2A is carboxy; (II) XA is S, YA is 2-acetylamino-2-methoxycarbonylethyl, Z1A and Z3A are hydrogen and Z2A is carboxy; (III) XA is S, YA are 2-acetylamino-2-carboxyethyl, Z1A and Z3A are hydrogen and Z2A is hydroxy; (IV) XA is S, YA is 2-acetylamino-3-oxo-3-. { 1- (2-methoxycarbonyl) pyrrolidinyl} propyl, Z1A and Z3A is hydrogen and Z2A is hydroxy; (V) XA is S, YA is 2-acetylamino-2-methoxycarbonylethyl, Z2A and Z3A combine together to form an unsubstituted benzene ring and Z1A is carboxy; and (VI) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z2A and Z3A combine together to form an unsubstituted benzene ring and Z1A is carboxy. 7) A 2,3-di-substituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: XB is S, 0 or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms (wherein at least one hydrogen may be optionally substituted with carboxy or a group derived therefrom or amino or a group derived therefrom); and ZB is carboxy, C00R3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms); carbon) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms). 8) A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, according to item 7) described above, wherein: XB is S; YB is a straight chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR6 (wherein R6 is an alkyl, an alkenyl or an alkynyl having 1 to 4 carbon atoms) or NR7R8 (wherein each of R7 and R8, which may be the same or different and independently represents hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 4 carbon atoms) at 5 carbon atoms), and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl 9) A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, according to item 8) described above , where: YB is 11-acetylamino-11-carboxy-n-undecyl; and ZB is carboxy 10) A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: XB is S, O or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms wherein at least one hydrogen is substituted with COW2. { wherein W2 is a saturated heterocyclic ring unsubstituted or substituted by carboxy, a hydroxyalkyl having 1 to 4 carbon atoms, phenyl or C00R9 (wherein R9 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms )} and at least one other hydrogen is substituted with NR10R11 (wherein each of RIO and Rll, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or a unsubstituted or substituted acyl having 1 to 5 carbon atoms); and ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms) carbon) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms). 11) A 2,3-disubstituted cyclopentanone derivative of the formula [IB] or a pharmacologically acceptable salt thereof, according to item 10) described above, wherein:? G TS f YB is a chain aliphatic hydrocarbon group linear or branched having 1 to 6 carbon atoms. { wherein a hydrogen is substituted with COW3 (wherein W3 is a 1-azetidinyl, 1-piperidyl, 1-pyrrolidinyl, 1-piperazinyl, or 4-morpholinyl group, which may be unsubstituted or substituted by carboxy, methoxycarbonyl, -hydroxyethyl, phenyl or tert-butoxycarbonyl) and the other one of the hydrogens is substituted with NHC0R12 (wherein R12 is an alkyl having 1 to 4 carbon atoms)}; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxy. 12) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 11) described above, wherein: XB is S; YB is 2-acetylamino-3-oxo-3- (1-pyrrolidinyl) propyl, 2-acetylamino-3-. { l- (2-methoxycarbon? l) pyrrole idinyl-3-oxopropyl, 2-acetylamino-3-oxo-3- (1-pipepdyl) propyl, 2-acet? lamino-3- (4-morpholinyl) -3-oxopropyl , 2-acetylamino-3-. { 1- (2-methoxycarbonyl) azetidinyl} -3-oxopropyl, 2-acetylamino-3-oxo-3- (l-piperazinyl) propyl, 2-acetylamino-3- [1 -. { 4- (2-Hydroxyethyl) piperazinyl} ] -3-oxopropyl, 2-acetylamino-3 -. { 1- (4-f-enylpiperazinyl)} -3-oxopropyl or 2-acetylamino-3-. { 1- (4-tert-butoxycarbonylpiperazinyl)} -3-oxopropyl; and ZB is carboxy or methoxycarbonyl. 13) A 2,3-disubstituted cyclopentanone derivative of a formula [IB] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: XB is S, O or SW; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein at least one hydrogen is substituted with NHCOV1 (wherein VI is an alkyl having from 2 to 5 carbon atoms and contains from 4 to 11 halogen atoms) and at least one of the hydrogens can be further substituted with carboxy or COOR13 (wherein R13 is an unsubstituted or substituted alkyl, alkenyl or alkynyl having from 1 to 4 carbon atoms)}; and ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms) carbon) or CH2OCOR5 (where R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms). «14) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described above in part 1) or a pharmacologically acceptable salt thereof, according to item 13) described above, wherein: XB is S; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein a hydrogen is substituted with NHC0V2 (wherein V2 is an alkyl having 2 to 5 carbon atoms and containing 4 to 11 fluoro atoms) and another one of the hydrogens is further substituted with carboxy or COOR13 '(in where R 13 'is an alkyl, alkenyl or alkynyl having from 1 to 4 carbon atoms)}; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl. 15) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 14) described above, wherein: YB is 2-carboxy-2- (pentafluoropropionyl) aminoethyl; and ZB is carboxy or hydroxymethyl. 16) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described above in item 1) above or a pharmacologically acceptable salt thereof, according to item 1) above, wherein XB is S, O or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein at least one hydrogen is substituted with an unsubstituted or substituted monocyclic aromatic heterocyclic ring and at least one of the hydrogens is further substituted with NR15R16 (wherein each of R15 and R16 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms)}; and ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted alkyl or substituted having 1 to 4 carbon atoms) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms). 17) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 16) described above, wherein: YB is an aliphatic hydrocarbon group of linear chain having 1 to 4 carbon atoms. { where a hydrogen can being substituted with an unsubstituted pyridine ring or • ^^^^^^^^^ -? -? Substituted with an alkyl having 1 to 4 carbon atoms or with 5-tetrazolyl, and another of the hydrogens can be further substituted with NHC0R17 (wherein R17 is an alkyl having 1 to 4 carbon atoms; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl 18) A 2,3-disubstituted cyclopentanone derivative of formula [IB] described in part 1 above or a pharmacologically acceptable salt thereof, according to item 17) described above, wherein: YB is 3- (3-pyridyl) propyl, 3 -. { 3 - (1-met ilpyridiniumiodide)} propyl or 2-acetylamino-2- (5-tetrazolyl) ethyl; ZB is carboxy or methoxycarbonyl. 19) A cyclopentanone derivative of formula [ÍC] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: ring A forms a conjugated oxo double bond together with the atom carbon bonded to CH2-XC-YC; Xc is S, O or SO; Yc is an aliphatic hydrocarbon group that has 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); and each of Zlc, Z2C and Z3C which may be the same or different and independently represents carboxy or a group derived therefrom, hydroxy or a group derived therefrom, amino or a group derived therefrom, an unsubstituted alkyl or substituted or alkenyl having from 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 20) A cyclopentanone derivative of formula [ÍC] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 19) described above wherein: ring A forms an oxo conjugated double bond together with the carbon atom bonded to CH2-XC-YC; Xc is S, O or SO; Y c is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR 1 (wherein R 1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 atoms carbon), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring 25 unsubstituted or substituted with carboxy or a group Jjjjjjjjjjl derived from the same or amino or a group derived therefrom), NR4R5 wherein each of R4 and R5 which may be the same or different and independently represents hydrogen, a unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or 0R6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 or to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and, each of Zlc, Z2C and Z3C independently represent carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 atoms of carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each one of R12 and R13 which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having from 1 to 5 carbon atoms ), 5-tetrazolyl, chlorine, f loror or hydrogen. 21) A cyclopentanone derivative of formula [ÍC] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 20) described above, wherein: ring A forms an oxo conjugated double bond together with the carbon atom bonded to CH2-XC-YC; ? p? S Yc is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (where at least two hydrogen atoms are substituted with carboxy, C00R1 '(where R' is an alkyl or alkenyl having 1 to 4 carbon atoms) carbon), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms) carbon), and each of Zlc, Z2C and Z3C is carboxy, COOR7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO1 is hydrogen or an acyl having from 1 to 5 carbon atoms) 22) A cyclopentanone derivative of formula [ÍC] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 21) described above, wherein: ring A forms a double bond conjugated with oxo without containing the carbon atom that is bound to CH2-XC- YC; ? ? S > "Yc is 2-acetylamino-2-carboxyethyl, and each of Zlc or Z2C is hydroxy and the remaining groups outside of Zlc, Z2C and Z3C are all hydrogen." 23) A cyclopentanone derivative of formula [IC] described in previous paragraph 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: ring A forms a double bond conjugated with oxo without containing the carbon atom bonded to CH2-XC-YC; Xc is S, O or SO; Yc is an aliphatic hydrocarbon group that has 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); and each of Zlc, Z2C and Z3C is carboxy or a derivative thereof, an unsubstituted or substituted alkyl or alkenyl, having 1 to 4 carbon atoms, hydroxy or a derivative thereof, amino or a derivative group therein, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 24) A cyclopentanone derivative of formula [ÍC] described above in part 1) or a pharmacologically acceptable salt thereof, according to item 23) described above, wherein: ^^ UZTJSA ^^^ ^^^ Ring A forms a double conjugated oxo bond without containing the carbon atom bonded to CH2-XC-YC; Xc is S, 0 or SO; Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms); carbon), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted by carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or unsubstituted or substituted acyl having 1 to 5 carbon atoms); and each of Zlc, Z2C and Z3C independently represent carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, a substituted or unsubstituted alkyl having 1 to 4 carbon atoms), carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represent hydrogen, a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having from 1 to 5 carbon atoms) , 5-tetrazolyl, chlorine, fl or and hydrogen. 25) A cyclopentanone derivative of formula [ÍC] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 24) described above, wherein: ring A forms a double bond conjugated with oxo without contains the carbon atom bonded to CH2-XC-YC; Á.Q s; Yc is an aliphatic hydrocarbon group that has 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1 '(wherein R1' is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which may be optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms), and, each of Zlc, Z2C and Z3C is carboxy, C00R7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO' is hydrogen or an acyl having 1 to 5 carbon atoms). Cyclopentanone derivative of the formula [I C] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 25) described above, wherein: ring A forms a conjugate bond with oxo without containing the carbon bonded to CH2-XC-YC; Yc is 2-acetylamino-2-carboxyethyl; and all of Zlc, Z2C and Z3C are hydrogen. 27) A ketone derivative of formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: AD is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, 0 or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is > - ^^^ - '^' ^ ite w ^ m ^ E substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom), -y, ZD is carboxy or a a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, an amino group or a derivative thereof, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 28) A ketone derivative of formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 27) described above, wherein: AD is an aliphatic hydrocarbon group having from 1 to 4 carbon atoms; BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms) carbon), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted by carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5 which may be the same or different and independently represent hydrogen, an alkyl not substituted or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or 0R6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 atoms d carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and ZD is carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, or an unsubstituted acyl or substituted having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which they may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chloro, fluorine or hydrogen. 29) A ketone derivative of formula [ID] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 28) described above, wherein: AD is an alkyl having 1 to 4 atoms of carbon; BD is hydrogen or an alkyl having 1 to 4 carbon atoms; XD is S; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1 '(wherein R1' is an alkyl or alkenyl having 1 to 4 carbon atoms). carbon), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which may be hydrogen optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms) ZD is carboxy, C00R7 '(wherein R7' is alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO' is a hydrogen or an acyl having 1 to 5 carbon atoms). 30) A ketone derivative of the formula [ID] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 29) described above, wherein: AD is methyl; BD is hydrogen; YD is 2-acetylamino-2-carboxyethyl or 2-acetylamino-2-methoxycarbonylethyl; and ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl. 31) A ketone derivative of formula [ID] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: AD is an unsubstituted or substituted aromatic hydrocarbon, a heterocyclic ring aromatic or a saturated heterocyclic ring; BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O, or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a derivative thereof or amino or a derivative thereof or hydroxy or a derivative thereof); and ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring , a halogen or hydrogen. & 2) &ei & £ i? ßss? 3 &¡ik & j 32) A ketone derivative of formula [ID] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 31) described above, wherein: AD is an unsubstituted benzene ring in which , when substituted by 1 to 3 hydrogen atoms are substituted with an unsubstituted or substituted alkyl group having from 1 to 4 carbon atoms, a halogen, hydroxy, an alkoxy having from 1 to 4 carbon atoms, amino, an alkyl or dialkylamino having 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms; carbon atoms, an acylamino that has 1 to carbon atoms, cyano or trifluoromethyl; BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O, or SO; YD is an aliphatic hydrocarbon group that has 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or 0R6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl unsubstituted or its constituted having 1 to 5 carbon atoms); and ZD is carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an acyl substituted unsubstituted having 1 to 5 carbon atoms), hydroxy, 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each R12 and R13, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen. 4 - 40 - 33) A ketone derivative of formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 32) described above, wherein: AD is an unsubstituted benzene ring or substituted in which, when 1 to 3 hydrogen atoms are substituted, they are substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, a halogen or trifluoromethyl; BD is hydrogen or an alkyl having 1 to 4 carbon atoms; XD is S; YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1 '(wherein R1' is alkyl or alkenyl having 1 to 4 carbon atoms) ), NHCOR14 (wherein each R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having from 1 to 4 carbon atoms); ZD is carboxy, COOR7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms), or CH2OR10 '(wherein each of RIO' is hydrogen or an acyl having 1 to 5 carbon atoms) 34) A ketone derivative of formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 33) described above, wherein: AD is a ring of unsubstituted benzene or a benzene ring substituted with methyl or methoxy; BD is a hydrogen; XJ-J is; YD 2-acetylamino-2-carboxyethyl, 2-acetylamino-2-methoxycarbonylethyl or 2-acetylaminoethyl; and, ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl. 35) A ketone derivative of formula [ID] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: AD and BD combine together for a cycloalkan-1 ring unsubstituted or substituted one having from 3 to 7 carbon atoms (except for 5 carbon atoms) 36) A ketone derivative of the formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof, of according to item 35) above, wherein: AD and BD combine together to form a cyclobutan-1-one ring or a substituted or unsubstituted cyclohexan-1-one ring; XD is S, 0 or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is unsubstituted or with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having from 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each R4 and R5 which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or 0R6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl which has 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) and ZD is carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms) , CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (where RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl which has 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen. 37) A ketone derivative of formula [ID] described in item 1 above or a pharmacologically acceptable salt thereof, according to item 36) described above, wherein: AD and BD combine together to form a cyclobutan-1 ring -one or a cyclohexan-1-one ring; XD is S; YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1 '(where R1' is an alkyl or alkenyl having 1 to 4 carbon atoms ), NHC0R14 (wherein R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms) carbon); ZD is carboxy, COOR7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO' is hydrogen or an acyl having 1 to 5 carbon atoms) . 38) A ketone derivative of formula [ID] described above in item 1) or a pharmacologically acceptable salt thereof according to item 37), wherein: (I) AD and BD combine together to form a cyclobutan ring -1-one, XD is S, YD is 2-acetylamino-2-carboxyethyl and ZD is carboxy; (II) AD and BD combine together to form a ring of cyclobutan-1-one, XD is S, YD is 2-acetylamino-2-methoxycarbonylethyl and ZD is methoxycarbonyl; 10 (III) AD and BD combine together to form a cyclohexane-1-one ring, XD is S, YD is 2,3-dihydroxy-n-propyl and ZD is acetoxymethyl; and (IV) AD and BD combine together to form a cyclohexan-1-one ring, XD is S, YD is 2-acetylamino-2-carboxyethyl and ZD is carboxy. 39) A β -disubstituted amino ketone derivative of formula [1F] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: AF is a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; BF is a hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XF and YF is a linear or branched chain aliphatic hydrocarbon group having from 1 to 10 carbon atoms »* (Wherein at least one hydrogen can optionally be substituted with carboxy or a group derived therefrom, amino or a group derived therefrom, hydroxy or a group derived therefrom) or; XF and YF are linked together directly or via a hetero atom to form a monocyclic heterocyclic ring (wherein at least one hydrogen atom may be optionally substituted with an alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 40) A β-disubstituted amino ketone derivative of formula [1F] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 39) described above, wherein: AF is methyl, ethyl, n-propyl or isopropyl, which may be unsubstituted or substituted; BF is hydrogen; each of XF and YF, which may be the same or different and independently represent an alkyl having 1 to 6 carbon atoms or XF and YF linked together directly or via a heteroatom to form a heterocyclic ring - 4-46. -monocyclic which can be unsubstituted or substituted with an alkyl having 1 to 4 atoms or phenyl; ZF is carboxy, C00R1 (wherein R1 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an alkyl having 1 to 4 carbon atoms), cyano, CH20R4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having from 1 to 5 carbon atoms), hydroxy, 0R5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having from 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms ), 5-tetrazolyl, chlorine or fluorine. 41) A β-disubstituted amino ketone derivative of formula [1F] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 40) described above, wherein: AF is methyl; BF is hydrogen; - 4T - XF and YF are both n-propyl, ethyl or isopropyl, XF and YF are linked to each other directly or via a heteroatom to form pyrrolidine, piperidine, morpholine, a 4-methylpiperazine ring or 4-phenylpiperazine; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms) or cyano. 42) A β-disubstituted amino ketone derivative of formula [1F] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 1) above, wherein: AF is an unsubstituted or substituted aryl, heteroaryl or a saturated heterocyclyl ring; BF is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms; XF and YF are a linear or branched aliphatic hydrocarbon group having from 1 to 10 carbon atoms (wherein at least one hydrogen may be optionally substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom), or XF and YF are joined together directly or via a heteroatom to form a heterocyclic ring (wherein at least one hydrogen can optionally be substituted with alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom, or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 43) A β-disubstituted amino ketone derivative of the formula [1F] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 42) described above, wherein: AF is a benzene ring or a heterocyclic ring unsubstituted or substituted monocyclic aromatic. BF is hydrogen; XF and YF, which may be the same or different, are a linear or branched aliphatic hydrocarbon group having 1 to 6 or XF and YF are linked together directly or via a heteroatom to form a heterocyclic ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, COOR1 (wherein R1 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted acyl or substituted having 1 to 5 carbon atoms), hydroxy, 0R5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms 0 an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently 0 represents hydrogen, an unsubstituted or substituted alkyl which has from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chloride or fluorine. 44) A β-disubstituted amino ketone derivative of formula 5 [1F] described above in item 1) or a pharmacologically acceptable salt thereof, according to item 43) described above wherein: AF is an unsubstituted or substituted benzene ring wherein, when substituted by 1 to 3 hydrogen atoms are 0 substituted with an alkyl having from 1 to 4 carbon atoms, a halogen, hydroxy, an alkoxy having from 1 to 4 carbon atoms, amino, an alkyl or dialkylamino having 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms, acylamino having from 1 to 5 carbon atoms, cyano or trifluoromethyl; BF is hydrogen; each of XF and YF, which may be the same independently and independently, represents an alkyl having 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom to form an unsubstituted monocyclic heterocyclic ring or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is a hydrogen or an alkyl having 1 to 4 carbon atoms), cyano or CH2OR4 '(wherein R4' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms) carbon). 45) A β-disubstituted amino ketone derivative of formula [1F] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 44) described above, wherein: AF is an unsubstituted or substituted benzene ring , wherein, when substituted by 1 to 3 hydrogen atoms are substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, halogen or trifluoromethyl; BF is hydrogen;^ - ^^^^^. ^^ T * XF and YF are both ethyl, n-propyl or isopropyl; or XF and YF are joined together directly or via a hetero atom to form a pyrrolidine, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring; ZF is carboxy, C00R1"(where Rl" is methyl or ethyl), CONR2"R3" (where R2"and R3", which may be the same or different and each is hydrogen, methyl or ethyl) or cyano. 46) A β-disubstituted aminoketone derivative of formula [1F] described above in item 1) or a pharmacologically acceptable salt thereof, according to the above item 1), wherein: AF and BF combine together to form a ring unsubstituted or substituted C.sub.1 -cycloalkan-1-one having from 3 to 7 carbon atoms or AF and BF combine together to form a c-cloalkan-1-one ring, having from 3 to 7 carbon atoms, in which, the ring is fused with an aromatic hydrocarbon or an aromatic heterocyclic ring. XF and YF are a straight or branched chain aliphatic hydrocarbon group having from 1 to 10 carbon atoms (wherein at least one hydrogen can be optionally substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom) or XF and YF are linked together directly or via a heteroatom to form a heterocyclic ring (wherein at least one hydrogen can be optionally substituted with an alkyl having from 1 to 4 carbon atoms). carbon, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 47) A β-disubstituted aminoketone derivative of the formula [1F] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 46) described above, wherein: AF and BF combine together to form a ring unsubstituted or substituted cycloalkan-1-one having 4 to 6 carbon atoms or to form an unsubstituted or substituted cycloalkan-1-one ring having 4 to 6 carbon atoms which is fused with an aromatic hydrocarbon or a monocyclic aromatic heterocyclic ring; each of XF and YF, which may be the same or different and independently is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom for forming a monocyclic heterocyclic ring, which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; - < $ F- zf is carboxy, COOR 1 (wherein R 1 is a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms 0 phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (in where R4 is a hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, 0R5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl not substituted or substituted having 1 to 5 carbon atoms, preferably an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently represent hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine or fluorine. 48) A β-disubstituted amino ketone derivative of formula [1F] described in the above item 1) or a pharmacologically acceptable salt thereof, according to item 47) described above, wherein: AF and BF combine together to form a unsubstituted or substituted cyclopentane-1-one ring or to form a ## STR3 ## - unsubstituted or substituted cyclopentan-1-one ring fused with benzene or a monocyclic aromatic heterocyclic ring; each of XF and YF, which may be the same or different and independently are an alkyl having 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom to form a monocyclic heterocyclic ring, the which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms), cyano or CH20R4 '(wherein R4' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms ). 49) A β-disubstituted aminoketone derivative of formula [1F] described in item 1) above or a pharmacologically acceptable salt thereof, according to item 48) described above, wherein: AF and BF combine together to form a ring cyclopentane-1-one or an indan-1-one ring; XF and YF are linked together directly or via a heteroatom to form a pyrrolidone, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring; Y "if" iB "fi1 '" íf-ÉÉÍt ZF is carboxy, C00R1"(where R" is methyl or ethyl), CONR2"R3" (where R2"and R3, which may be the same or different and each one is hydrogen, methyl or ethyl) or cyano 50) A pharmaceutical composition comprises as an effective ingredient a cyclopentanone derivative of formula [ÍA] according to item 1) above or a cyclopentanone derivative according to any of the items 2) to 6) described above or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl, and Z3A is methoxycarbonyl, (2) when Z1A and Z2A is hydrogen, XA is O or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl, (3) XA is N or O, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A and s phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen. 51) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a cyclopentanone derivative of formula [ÍA] according to item 1) above or a cyclopentanone derivative according to any of items 2) to 6 ) described above, or a pharmacologically acceptable salt wherein the cyclopentanone derivative further includes: 1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and Z3A is methoxycarbonyl, 2) when ZlA and Z2A are hydrogen, XA is O or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; 3) XA is N or 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; 4) XA is 0, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A and amino or a group derived therefrom; 5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen. 52) A composition for the treatment of nervous diseases of the peripheral system comprises a cyclopropane derivative as an effective ingredient of formula [ΔA] of t .- ^ ^ Aifea according to clause 1) above or cyclopentanone derivative of any of items 2) to 6) described above or a pharmacologically acceptable salt thereof, wherein the cyclopropane derivative further includes: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and Z3A is methoxycarbonyl, (2) when Z1A and Z2A are hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or O, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is 0, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-1-phenylmethylthio and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen; 53) A composition for promoting cell differentiation of nerves, comprising as an effective ingredient a cyclopropane derivative of formula [IA] according to item 1) above or a cyclopropane derivative according to any of items 2) to 6) described above or a pharmacologically acceptable salt thereof, wherein the cyclopropane derivative further includes: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and Z3A is methoxycarbonyl, (2) when Z1A and Z2A they are hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is 0, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen. 54) A pharmacological composition comprising as an effective ingredient a 2,3-disubstituted cyclopentanone derivative of formula [IB] described in item 1) above or a 2,3-disubstituted cyclopentanone derivative according to any of the items 7) to 18) according to the aforementioned paragraph or a pharmacologically acceptable salt thereof. 55) A composition for the treatment of diseases of the central nervous system comprising a 2,3-disubstituted cyclopentanone derivative as an effective ingredient of formula [IB] described in part 1) above or a 2,3-di-substituted cyclopentanone derivative according to to any of items 7) to 18) described above or a pharmacologically acceptable salt thereof. 56) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a 2,3-di-substituted cyclopentanone derivative of the formula [IB] described in item 1) above or a 2,3-disubstituted cyclopentanone derivative according to any one of items 7) to 18) or a pharmacologically acceptable salt thereof. 57) A composition for promoting nerve cell differentiation comprising as an effective ingredient a 2,3-disubstituted cyclopentanone derivative of formula [IB] described in item 1) above or a 2,3-di-substituted cyclopropane derivative according to any of items 7) to 18) or a pharmacologically acceptable salt thereof. 58) A pharmacological composition comprising as an effective ingredient a cyclopentanone derivative of formula [ÍC] described in item 1) above or a cyclopentanone derivative according to any of items 19) to 26) or a pharmacologically acceptable salt thereof, wherein the derivative of üafejiiÉ? Stoíü ^ cyclopentanone also includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 59) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a cyclopentanone derivative of the formula [ÍC] described in item 1) above or a cyclopentanone derivative according to any of the items 19) a 26) described above, or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 60) A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a cyclopentanone derivative of formula [ÍC] described in item 1) above or a cyclopentanone derivative according to any of items 19) to 26) described above or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen or a hydroxy or a group derived therefrom. 61) A composition for promoting nerve cell differentiation comprising as an effective ingredient a cyclopentanone derivative of formula [ÍC] described in item 1) above or a cyclopentanone derivative according to any of items 19) to 26) described above or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 62) A pharmacological composition comprising as an effective ingredient a ketone derivative of formula [ID] according to item 1) above or a ketone derivative according to any of items 26) to 38) described above or a pharmacologically acceptable salt thereof, wherein AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes from (1) to (4): (1) XD is 0, YD is methyl, n-octyl or hexadecyl and ZD is methoxycarbonyl; (2) XD is 0, YD is benzyl and ZD is benzyloxymethyl; (3) XD is 0, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is 0, YD is trityl and ZD is trityloxymethyl and when AD is a substituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 63) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a ketone derivative of formula [ID] according to item 1) above or a ketone derivative according to any of item 26) 38) described above or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes subparagraphs (1) to (4): (1) XD is 0, YD is methyl, n-octyl or n- hexadecyl and ZD is methoxycarbonyl; (2) XD is O, YD is benzyl and ZD is benzyloxymethyl; (3) XD is 0, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 64) A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a ketone derivative of the formula [ID] according to item 1) above or a ketone derivative according to any of items 26) to 38 ) described above or a pharmacologically acceptable salt thereof, wherein when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes the subparagraphs (1) to (4): (1) XD is 0, YD is methyl, n-octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is O, YD is benzyl and ZD is benzyloxymethyl; (3) XD is O, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is 0, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 65) A composition for promoting nerve cell differentiation comprising as an effective ingredient a ketone derivative of formula [ID] according to item 1) above or a ketone derivative according to any of items 26) to 38) described above or a pharmacologically acceptable salt thereof, wherein AD and BD combine together to form a cyclobutane ring, the ketone derivative further includes subparagraphs (1) to (4): (1) XD is 0, YD is methyl, n-octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is O, YD is benzyl and ZD is benzyloxymethyl; (3) XD is 0, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is 0, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 66) A pharmacological composition comprising as an effective ingredient a compound of formula [ÍE] according to item 1) above or a pharmacologically acceptable salt thereof. 67) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a compound of formula [ÍE] according to item 1) above or a pharmacologically acceptable salt thereof. 68) A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a compound of formula [ÍE] according to item 1) above or a pharmacologically acceptable salt thereof. 69) A composition for promoting nerve cell differentiation comprising as an effective ingredient a compound of formula [ÍE] according to item 1) above or a pharmacologically acceptable salt thereof. 70) A pharmacological composition comprising as an effective ingredient a β-disubstituted aminoketone derivative of formula [1F] according to item 1 above or a β-disubstituted amino ketone derivative according to any of items 39) ~ 49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further includes those wherein BF is hydrogen, XF is directly attached to YF to form a piperidine and ZF ring It is carboxy. - - **.% *** £ :. 71) A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a β-disubstituted amino ketone derivative of formula [1F] according to item 1) above or a β-disubstituted amino ketone derivative according to any of the clauses 39) ~ 49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further includes those wherein BF is hydrogen, XF is directly attached to YF to form a peripheral ring and ZF is carboxy. 72) A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a β-disubstituted amino ketone derivative of formula [1F] according to item 1) above or a β-disubstituted amino ketone derivative according to any of the indents 39) ~ 49) described above or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring the β-disubstituted amino ketone derivative further includes those wherein BF is hydrogen, XF is directly attached to YF for forming a pipepdine ring and ZF is carboxy. 73) A composition for promoting nerve cell differentiation comprising as an effective ingredient a β-disubstituted aminoketone derivative of formula [1F] according to item 1) above or a β-disubstituted amino ketone derivative according to any of the items 39) 49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further include those wherein BF is hydrogen, XF is directly attached to YF to form a piperidine ring and ZF is carboxy; Brief Description of the Drawings Figure 1 shows the infrared absorption spectrum of NA32176A (compound of formula [ÍE]) measured using a potassium bromide tablet. Figure 2 shows the nuclear magnetic resonance spectrum of the hydrogen of NA32176A (compound of formula [ÍE]) as measured in heavy water. Figure 3 shows the nuclear magnetic resonance spectrum of the hydrogen of NA32176A (compound of formula [ÍE]) measured in heavy water.

Mode of carrying out the invention The compounds of the present invention represented by the formulas [ÍA], [IB], [ÍC], [ID], [ÍE] and [1F] show a promoter activity of neuronal differentiation and can be used as a medicament for the treatment of nervous disorders in the peripheral and central nervous system.

The compounds of the present invention are described below in more detail. [A] Compounds of formula [1A1 In the general formula [ÍA], XA is preferably O, S or SO, more preferably S. The straight or branched chain aliphatic group having from 1 to 20 carbon atoms, which is shows by YA in the general formula [ÍA], referring to an alkyl or alkenyl having from 1 to 20 carbon atoms, preferably an alkyl having from 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl , n-butyl, n-pentyl, n-hexyl, isopropyl or tert-butyl, more preferably a straight chain aliphatic group having 1 to 4 carbon atoms, more preferably ethyl. The aliphatic group can be unsubstituted or substituted. When the aliphatic group is substituted there may be present in the aliphatic group 1 to 6, preferably 1 to 3 substituents.

Examples of such substituents may be carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom. In the monocyclic aromatic heterocyclic ring and aromatic hydrocarbon have 3 to 6 carbon atoms in the general formula [IA], the aromatic hydrocarbon group is preferably a benzene ring and a monocyclic aromatic heterocyclic ring referring to a ring of 5 or 6 members which they contain a nitrogen, oxygen or sulfur atom. Where these groups substitute, for example the substituents are the same as those provided for the aliphatic group. The carboxy derivative group includes a carboxy functional group such as an esterified or amidated carboxy, cyano, hydroxymethyl or aminomethyl group formed by reduction of these functional groups and functional groups derived therefrom by modification similar to acylation of the functional groups. Preferably, the carboxy and the group derived therefrom include carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl, alkynyl or alkenyl having 1 to 4 carbon atoms), and COW (wherein W is a heterocyclic ring) unsubstituted or substituted saturated The alkyl, alkenyl or alkynyl shown by R1 for C00R1 may be straight chain, branched or cyclic When R1 is substituted from 1 to 6, preferably from 1 to 3 the substituents may be present in R1 and examples of the substituents are halogen, hydroxy, carboxy, methoxycarbonyl, cyano and acetylamino, R1 is preferably unsubstituted, Examples of the alkyl groups are methyl, ethyl, ethylene, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, ter- butyl, and cyclobutyl, preferably methyl, ethyl, ethylene and n-propyl, more preferably methyl Example of the alkenyl group are vinyl, 2-propenyl, isopropenyl and 2-butenyl A typical example of the alkynyl group is 2 -propeny ilo. W represents a heterocyclic ring, preferably a saturated heterocyclic ring, more preferably an azetidine, piperidine, pyrrolidine, morpholine or piperazine ring. These heterocyclic rings can be attached to a carbonyl via a carbon or nitrogen atom, preferably bonded to a carbonyl via a nitrogen. Where the heterocyclic ring is substituted from 1 to 4, preferably from 1 to 2 substituents may be present in each ring. Preferred examples of the substituents are carboxy and a group derived therefrom, more preferably carboxy and C00R11 (wherein Rll is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms); in this case examples of the alkyl and substituents where the alkyl is substituted is the same as in R1 described above). Examples of the amino derivative group include such functional groups that the amino is alkylated, acylated or sulfonated, nitro, hydroxyamino, imino and a heterocyclic group containing the amino nitrogen atom, preferably a group shown by NR2R3 (wherein each of R2 and R3, which may be the same or different independently, represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms). In the group shown by NR2R3, the alkyl for R2 and R3 and the substituent where the alkyl is substituted by it as in Rl. The acyl for R2 and R3 can be straight chain, branched, cyclic, saturated or unsaturated. Where the acyl is substituted, the substituents are the same as in Rl. More preferably the amino derivative group is represented by NHCOR12 (wherein R12 is an alkyl having from 1 to 4 carbon atoms and examples of R12 is the same as in R1) and more preferably R12 is methyl. Examples of the hydroxy derivative group include a functional group in which the hydroxy is alkylated or acylated, for example, OCOR14 (wherein the functional group alkylated at R14 is an unsubstituted or substituted alkyl and examples of the alkyl is the same as in R1 and the functional group acylated at R14 is an unsubstituted or substituted acyl and examples of the acyl are the same as in R2), a keto or a halogen. Each of Z1A, Z2A and Z3A in the compound of formula [IA] represent carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a derivative thereof, amino or a group derived therefrom, sulfate or a group derived therefrom, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; or Z2A and Z3A combine together to form an unsubstituted or substituted aromatic hydrocarbon or an aromatic heterocyclic ring; in this case Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, halogen or hydrogen. Examples of the sulfate derivative group are sulfonamide derivative groups, such as S02NH2, and S02NHCH3, S02N (CH3) 2 and S02NHCOCH3. Examples of the phosphate derivative group are P (0) (OH) H, P (0) (OH) (NH 2) and P (0) (OH) CH (OCH 3) 2. Examples of the groups derived from carboxy, hydroxy and amino are the same as described above. Examples of the amino derivative group further include NHS02Ph, NHCOCF3, NHCOC2F5, NHS02CF3, and NHS02C2F5. Preferred examples of Z1A, Z2A and Z3A include carboxy, C00R4 (wherein R4 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each R8 and R9, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 at 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl not replaced or substituted that has 1 to 5 carbon atoms), 5-tetrazolyl, a halogen or hydrogen. Examples of the unsubstituted or substituted alkyls having from 1 to 4 carbon atoms, mentioned above are alkyl shown by R, R5, R6, R7, R8, R9 and RIO and the substituents when these groups are »2 substituted are the same as in Rl. Examples of acyl shown by R7, R8, R9 or RIO and the substituent when these groups are substituted by the same as in R2. Specific examples of the acyl are acetyl, propionyl, acryloyl, propioloyl, n-butyryl, isobutyryl, crotonyl, valeryl, isovaleryl and pivaloyl, preferably acetyl, propionyl, acryloyl and propioloyl, more preferably acetyl. A particularly preferred combination of R8 and R9 is that R8 is hydrogen and R9 is acetyl. Examples of halogen are fluorine, chlorine, bromine and iodine, Preferably fluorine and chlorine. Preferred examples of substituents for Z1A, Z2A and Z3A are the case where one or two substituents other than hydrogen, more preferably, substituents such as carboxy, C00R4, OCOR13 (wherein R13 is an alkyl having 1 to 4 carbon atoms) and examples of the Alkyl are the same as in those of Rl), hydroxy and CH2OR10, more preferably carboxy, methoxycarbonyl, hydroxymethyl, hydroxy and acetyloxymethyl. Examples of the aromatic hydrocarbon formed by combination of Z2A and Z3A are a benzene ring and a ring naphthalene. Examples of the aromatic heterocyclic ring formed by Z2A and Z3A are a 6-membered heteroaryl such as a pyridine, pyrazine or pyrimidine ring and a 5-membered aromatic heterocyclic ring such as a thiophene, pyrrole, furan, oxazole, thiazole, isoxazole, isothiazole or azol rings Preferably, the group formed by Z22 and Z3A is a hydrocarbon aromatic, more preferably a benzene ring. Examples of the substituents are the same as in those of Z, when the ring is substituted. Preferred examples of the substituents include an alkyl having from 1 to 4 carbon atoms, preferably, methyl, ethyl, n-propyl and isopropyl, which may be unsubstituted or substituted by a halogen (for example fluorine) such as a trifluoromethyl; an alkyloxy having 1 to 4 carbon atoms such as methoxy and ethoxy; nitro and halogen, for example fluorine, chlorine or bromine. [B] Compounds of formula flB] In the compounds of the present invention represented by the formula [IB], XB ?? is preferably S, O or SO, more preferably S. The straight or branched chain aliphatic hydrocarbon group having 7 to 20 carbon atoms, which is shown by YB, refers to an alkyl or alkenyl having 7 to 20 carbon atoms. Examples of the alkyl or alkenyl are n-pentyl, n-octyl, n-nonyl. n-decanyl, n-undecanyl, n-dodecanyl, n-tridecanyl, n-tetradecanyl, n-pentadecanyl, n-dodecanyl, n-hexadecanyl, n-pentadecanyl and n-octadecanyl, preferably an alkyl having from 7 to 15 atoms of carbon, more preferably n-dodecyl. The aliphatic hydrocarbon group can be unsubstituted or substituted. Where the aliphatic hydrocarbon group is substituted, the aliphatic group may have, for example, 1 to 6, preferably 1 to 3 substituents thereon. Such substituents are carboxy or a group derived therefrom, amino or a group derived therefrom, hydroxy or a group derived therefrom. The carboxy derivative group includes a functional carboxy group such as an esterified or amidated carboxy group, cyano, hydroxymethyl or aminomethyl formed by reduction of functional groups and functional groups derived therefrom, by acylation-like modification of the functional groups. Preferably, carboxy and the group derived from The same includes carboxy and C00R6 (wherein R6 is an unsubstituted or substituted alkyl, alkenyl or alkynyl having from 1 to 4 carbon atoms). The alkyl, alkenyl or alkynyl shown for R6 in C00R6 can be linear, branched or cyclic. Examples of the substituents are a halogen, hydroxy, carboxy methoxycarbonyl, cyano and acetamido wherein R6 is substituent. R6 is preferably unsubstituted. Examples of the alkyl group are methyl, ethyl, ethynyl, n-propynyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tertbutyl and cyclobutyl, preferably methyl, ethyl, ethylene and n-propyl. Examples of the alkenyl group are vinyl, 2-propenyl, isopropenyl and 2-butenyl. A typical example of the alkynyl group is 2 -propenyl. Examples of the amino derivative group include functional groups such that the amino is alkylated, acylated or sulphonated, nitro, hydroxyamino, imino a and heterocyclic group Containing the amino nitrogen atom, preferably a ^^^ A ^^^^^ group shown by NR7R8 (wherein each R7 and R8, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms). In the group shown by NR7R8, the alkyl for R7 and R8 and the substituents where the alkyl is substituted by the same as in R6. The acyl for R7 and R8 can be linear, branched, cyclic, saturated or unsaturated. When the acyl is substituted, the substituent is the same as in R6. Representative examples of the acyl are acetyl, propionyl, acryloyl propioloyl, n-butyryl, isobutyryl, crotonyl, valeryl, isovaleryl and pivaloyl preferably acetyl, propionyl, acryloyl and propionyloyl, more preferably acetyl. A particularly preferred combination of R7 and R8 is that R7 is hydrogen and R8 is acetyl. Examples of the hydroxy derivative group include a functional group in which the hydroxy is alkylated or acylated, for example, 0C0R14 (wherein the functional group alkylated at R14 is unsubstituted or substituted alkyl and examples of the alkyl are the same as in R6 and the functional group acylated in R14 is an unsubstituted or substituted acyl and examples of the acyl are the same as in R7), a keto and a halogen. In the compounds of general formula [IB], the straight or branched chain aliphatic group of 1 to 6 carbon atoms, which is substituted with COW, is exemplified by methyl, ethyl, n-propyl, n-butyl, n- pentyl, n-hexyl, isopropyl and tertbutyl, preferably a linear aliphatic group having 1 to 4 carbon atoms, more preferably ethyl. In the aliphatic group, at least one hydrogen, preferably one hydrogen, can be substituted with COW. W represents an unsubstituted or substituted heteroaryl or a saturated aromatic heterocyclic ring, preferably a saturated aromatic heterocyclic ring, more preferably an azetidine, piperidine, pyrrolidine, piperazine or morpholine ring. These heterocyclic rings can be attached to a carbonyl via a carbon or nitrogen atom, preferably via a nitrogen. When the heterocyclic ring is substituted, each ring may have 1 to 4, preferably 1 to 2 substituents thereon. Preferred examples of the substituents are carboxy, a hydroxyalkyl having 1 to 4 carbon atoms, phenyl or C00R9 (wherein R9 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, in this case, examples of the alkyl and substituents where the alkyl is substituted is the same as in R6 described above). Examples of the hydroxyalkyl are 2-hydroxyethyl, 3-hydroxypropyl and 4-hydroxybutyl, preferably 2-hydroxyethyl. C00R9 is preferably terbutoxycarbonyl. In C00R9, at least one hydrogen, preferably a hydrogen, can be substituted with amino or a group derived therefrom. Examples of the amino derivative group - = & "" & = s5¡iES - á d are the same as described above, preferably NR10R11 (wherein each of RIO and Rll, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms.) In the group shown by NR 10 R 11, examples of the alkyl and substituents in which the alkyl is substituted are the same as those provided for R. In the group shown by NR10R11, the acyl for RIO and Rll can be linear, branched, cyclic, saturated or unsaturated. When the acyl is substituted, the substituents are the same as those provided for R6, preferably NHCOR12 (wherein R12 is an alkyl having 1 to 4 carbon atoms and examples of the alkyl are the same as those provided. of general formula [IB], examples of the straight or branched chain aliphatic group having 1 to 6 carbon atoms and substituted with NHCOV1 are methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl and tertbutyl, preferably a linear aliphatic group having 1 to 4 carbon atoms, more preferably ethyl In the aliphatic group, at least one hydrogen, preferably one hydrogen can be substituted with NHCOVl. 2 to 5 carbon atoms, which contain 4 to 11 halogen atoms Example of halogen are fluorine, chlorine, bromine and iodine, particularly fluorine Specific examples of the substituted NHC0V1 alkyl is tetr afluoroethyl, heptafluoro-n-propyl, nonafluoro-n-butyl and undecafluoro-n-pentyl. In this aliphatic hydrocarbon group, at least one hydrogen, preferably a hydrogen, can be substituted with carboxy or a group derived therefrom. Examples of the carboxy derivative group are the same as those described above, preferably carboxy or C00R13 (wherein R13 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, an alkenyl or an alkynyl and examples of these groups are the same as those provided for R6), more preferably carboxy. In YB of the compounds represented by the general formula [IB], the aryl has from 3 to 6 carbon atoms referring to for example, a benzene ring and the monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms, referring to to a ring of 5 or 6 members that contain nitrogen, oxygen or sulfur. When the aromatic hydrocarbon ring or monocyclic aromatic heterocyclic ring is substituted, examples of such substituents are the same as those provided for the above aliphatic group. In YB in the compound represented by the general formula [IB], the straight or branched chain aliphatic group having 1 to 6 carbon atoms having 1 to 6 carbon atoms, which is substituted with an aromatic heterocyclic ring monocyclic, is exemplified by methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl and tertbutyl, preferably a linear aliphatic group having from 1 to 4 carbon atoms, more preferably ethyl and n- propyl. In the aliphatic hydrocarbon group, at least one hydrogen, preferably a hydrogen, may be substituted with a monocyclic aromatic heterocyclic ring. Examples of the monocyclic aromatic heterocyclic ring are a ring of pyridine, pyrazine, pyrimidine, indole, pyrrole, imidazole, triazole, tetrazole, furan and thiophene, preferably pyridine or tetrazole. These heterocyclic rings can be linked by the aliphatic group via a carbon or nitrogen, preferably via a carbon. Therefore, where the heterocyclic ring is substituted, each ring may have from 1 to 4, preferably 1 or 2 substituents thereon. Examples of the substituents are an alkyl having 1 to 4 carbon atoms, preferably methyl. In this aliphatic group, at least one hydrogen, preferably one hydrogen may be substituted with amino or a group derived therefrom. Examples of the amino derivative group are the same as described above, preferably NR15R16 (wherein each of R15 and R16, which may be the same or different independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms). In the group shown ^ fjiBr NR15R16, examples of the alkyl and substituents where the alkyl is substituted is flB the same as those provided for R6. The acyl can be linear, branched, cyclic, saturated or unsaturated. Therefore, where the acyl is substituted, the substituent is the same as those provided for R6, preferably NHCOR17 (wherein R17 is an alkyl having 1 to 4 carbon atoms and examples of the alkyl are the same as those provided for R6). 10 In the compounds represented by the general formula [IB], ZB is carboxy or a group derived therefrom, sulfate or a group derived therefrom, phosphate or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy, ORÍ ( wherein R1 is an unsubstituted alkyl or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NHCOR 2 (wherein R 2 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms) carbon), NHS02R2 '(wherein R2' is a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms) Carbon or phenyl), a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. Examples of the carboxy derivative group are the same as those described above. Examples of the sulfate derivative group are sulfonamide derivative groups, such as S02NH2, S02NHCH3, S02N (CH3) 2 and S02NHC0CH3. Examples of the The group derived from phosphate are P (0) (OH) H, P (O) (OH) (NH2) and P (0) (OH) CH (OCH 3) 2. Examples of the alkyl having 1 to 4 carbon atoms, the alkyl shown by R 1, R 2 and R 2 'and the substituents when this alkyl group is substituted are the same those provided for R6. Examples of the acyl in R 1 and the substituents when the acyl is substituted is the same as those provided for R 7. Examples of NHC0R2 are NHCOCH3, NHCOCF3 and NHCOC2F5. Examples of NHS02R2 'are NHS02Ph, NHS02CF3 and NHS02C2F5. A preferred example of the monocyclic heteroaryl is 5-tetrazolyl. In ZR, example of the halogen is fluorine, chlorine, bromine and iodine, preferably fluorine and chlorine. Preferred examples of Z are carboxy, COOR3 (wherein R3 is a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms and examples of the alkyl and substituents on the alkyl are those provided for R6), CH2OR4 (wherein R4 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms and examples of the alkyl and substituents on the alkyl are those provided for R6), and CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms and examples of the alkyl and substituents on the alkyl are those provided for R6), more preferably carboxy, methoxycarbonyl, hydroxymethyl and acetyloxymethyl. [C] Compounds of formula FlC] In the present invention, ring A in the compounds represented by the general formula [1C] which represents a 2-cyclopenten-1-one ring, which includes cases in which the YC- XC-CH2 are attached to the carbon with a double bond and the carbon with a single bond. In the compound of the present invention represented by the formula [ÍC], Xc is preferably S, O or SO, more preferably S. In Yc in the compounds represented by the general formula [ÍC], the straight or branched chain aliphatic group it has from 1 to 6 carbon atoms including an alkyl or an alkenyl. Examples of the alkyl are methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl and tert-butyl. Examples of the alkenyl are vinyl, 2-propenyl, isopropenyl and 2-butenyl. Preferably the aliphatic hydrocarbon group is an alkyl having 1 to 4 carbon atoms, more preferably ethyl. The aliphatic hydrocarbon group may be unsubstituted or substituted. When the aliphatic hydrocarbon group is substituted, it may contain 1 to 6, preferably 1 to 4 substituents. As such substituents these are carboxy or a group derived therefrom, amino or a group derived therefrom and hydroxy or a group derived therefrom. The aromatic hydrocarbon ring or monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms referring to an aromatic hydrocarbon ring such as a benzene ring and an aromatic heterocyclic ring such as a 5 or 6 membered ring containing nitrogen, oxygen or sulfur. Where the aromatic hydrocarbon ring or an aromatic heterocyclic ring is substituted, examples of such substituents are the same as those provided for the aliphatic hydrocarbon group. The carboxy derivative group includes a functional carboxy group such as an esterified or amidated carboxy, cyano, hydroxymethyl or aminomethyl group formed by reduction of these functional groups and functional groups derived therefrom by modification similar to acylation or alkylation of the functional groups. Preferably, the carboxy and the group derived therefrom includes carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3, which may they are the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), and COW (W represents a saturated or unsaturated heterocyclic ring). Here the alkyl shown by R1 for COOR1 can be linear, branched or cyclic. Examples of the alkyl group are methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tertbutyl and cyclobutyl, preferably methyl, ethyl and n-propyl and more preferably methyl. Examples of the alkenyl are vinyl, 2-propenyl, isopropenyl and 2-butenyl. When replacing for example 1 to 6, preferably 1 to 3 substituents may be present. Examples of the substituents are halogen, hydroxy, thiol, carboxy, methoxycarbonyl, acetyloxy, acetylthio, cyano and acetylamino.

Examples of halogen are bromine, chlorine and fluorine. Preferably, the substituents on Rl are substituted. When the alkyl shown by R2 and R3 and these substituents are substituted, for example such substituents are the same as those provided for Rl. Preferably W represents a saturated heterocyclic ring, more preferably, an azetidine, piperidine, pyrrolidine, piperazine or morpholine ring. These heterocyclic rings can be bonded to carbonyl via carbon or nitrogen, preferably bonded to carbonyl via nitrogen. Where the heterocyclic ring is substituted 1 to 4, preferably 1 to 2 substituents may be present in each ring. Examples of the substituents are carboxy or a group derived therefrom and amino or a group derived therefrom. Examples of these groups are described in the specification. Examples of the amino derivative groups include such functional groups wherein the amino is alkylated or acylated, nitro, hydroxyamino, imino and a heterocyclic group containing the amino nitrogen atom, preferably a group shown by NR4R5 (wherein each one of R4 and R5, which may be different or the same and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms ). In the group shown by NR4R5, the alkyl for R4 and R5 and the substituents where the alkyl is substituted is the same as that in RI. The acyl for R 4 and R 5 can be linear, branched, cyclic, saturated or unsaturated. Representative examples of the acyl are acetyl, propionyl, acroyl, propioloyl, n-butyl, isobutyryl, crotonyl, valeryl, isovaleryl and pivaloyl. Where the acyl is substituted, the substituents are the same as those in Rl. Preferably, the amino group derivative is NHC0R14 (wherein R14 is an alkyl having from 1 to 4 carbon atoms in which the hydrogens can be substituted with fluorine, examples of the alkyl being the same as in those in R1). The number of fluorine atoms which may be substituted is 1 to 9, preferably 1 to 7. More preferably, R 14 is methyl. Examples of the hydroxy derivative group include a functional group in which the hydroxy is alkylated or acylated, a keto and a halogen, preferably 0C0R15 (wherein R15 is an alkyl having from 1 to 4 carbon atoms and examples of the alkyl they are the same to those in Rl). In the cyclopentanone derivative of general formula [IC], each of Zlc, Z2C and Z3C represents carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derivative thereof, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. Examples of the group derived from carboxy, amino or hydroxy are the ¡HAME as described above. Examples of alkyl and alkenyl and substituents when the alkyl and alkenyl are substituted thereto as those provided for A. Preferred examples of Z1C, Z2C and Z3C are carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, hydroxy, CH2OR10 (wherein RIO is a hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) carbon), 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be different or the same and independently represents a hydrogen , an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chloro, fluoro or hydrogen. The alkyl for R7, R8, R9, RIO, Rll, R12 and R13 and substituents, when the alkyl being substituted is the same as those provided for Rl. further, the acyl for RIO, R12 and R13 and the substituent when the substituted acyl is the same as those provided for R4. The preferred combination of R12 and R13 is that R12 is a hydrogen and R13 is acetyl. Examples of the halogen are fluorine, chlorine, bromine and iodine, preferably fluorine and chlorine. Preferred examples of the substituents Zlc, Z2C, and Z3C is the case that all substituents are hydrogen or that one or two are substituents other than hydrogen. More preferred examples of the substituents are, except for hydrogen, carboxy, C00R7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) and CH2OR10 '(wherein RIO' is hydrogen, an unsubstituted acyl or substituted having 1 to 5 carbon atoms). Examples of R7 'is the same as those provided for Rl. Examples of the acyl in RIO 'is the same as those provided for R4, more preferably, carboxy, methoxycarbonyl, hydroxymethyl and acetyloxymethyl. [D] Compounds of formula [ID] In the ketone derivative of the present invention represented by the general formula [ID], the unsubstituted or substituted aliphatic hydrocarbon group has from 1 to 4 carbon atoms, which is shown by AD , referring to an alkyl or alkenyl having 1 to 4 carbon atoms, which may be optionally substituted. Examples of the alkyl group are methyl, ethyl, n-propyl, n-butyl, isopropyl, cyclopropyl and tert-butyl. Examples of the alkenyl are vinyl, 2-propenyl, isopropenyl and 2-butenyl. Preferably, the aliphatic hydrocarbon group is exemplified by methyl, ethyl, n-propyl and isopropyl, more preferably methyl. The aliphatic hydrocarbon group may be unsubstituted or substituted. They may be present when the aliphatic group is substituted, for example, 1 to 6, preferably 1 to 3 substituents. Examples of the substituents are a halogen, hydroxy, thiol, carboxy, methoxycarbonyl, acetoxy, acetylthio, cyano and acetylamino.

= Fc? É »É¡ .i? Examples of halogen are bromine, chlorine and fluorine. Preferably, the aliphatic hydrocarbon group is substituted. The unsubstituted or substituted aromatic hydrocarbon ring, an aromatic heterocyclic ring or a saturated heterocyclic ring shown by AD in the compound of general formula [ID] is exemplified by a ring benzene, 1-naphthalene, 2-naphthalene, thiophene, furan, pyrrole , imidazole ring, oxazole, pyrazole, isoxazole, pyridine, pyrazine, indan, quinoline, isoquinoline, quinazoline, coumarin, pyrrolidine, piperidine or piperazine, preferably a benzene ring and a monocyclic aromatic heterocyclic ring, more preferably a benzene ring. These rings can be substituted or unsubstituted. When replacing 1 to 6, preferably 1 to 3 substituents may be present in each ring. Example of the substituent includes an alkyl having from 1 to 4 carbon atoms, halogen, hydroxy, alkyloxy having from 1 to 4 carbon atoms, amino, an aminoalkylamino or dialkylamino having from 1 to 4 carbon atoms, thiol, carboxy , an alkyloxycarbonyl having from 1 to 4 carbon atoms, an acyloxy having from 1 to 5 carbon atoms, an acylthio having from 1 to 5 carbon atoms, an acylamino having from 1 to 5 carbon atoms, cyano and trifluoromethyl. Examples of halogen are bromine, chlorine and fluorine. Examples of the alkyl having 1 to 4 carbon atoms and the alkyl portion in the acyl having 1 to 5 carbon atoms are the same as those provided for A. Preferred examples of AD are those unsubstituted or those substituted with methyl , methoxy, methoxycarbonyl, nitro, cyano, a halogen or trifluoromethyl, for 1 to 3 hydrogen atoms. In the ketone derivative of formula [ID], examples of the unsubstituted or substituted aliphatic group BD having 1 to 4 carbon atoms are the same as those provided for AD, preferably hydrogen or methyl. In the ketone derivative of general formula [ID], AD and BD are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having from 3 to 7 carbon atoms (with the proviso that a 5-atom ring is excluded) and examples of such rings include a ring of cyclopropanone, cyclobutanone, cyclohexanone and cycloheptanone, preferably a ring of cyclobutanone and cyclohexanone. The cycloalkan-1-one ring can be unsubstituted or substituted, except for the substitution in the general formula [ID]. When the ring is substituted 1 to 4, preferably 1 or 2 substituents may be present in each ring. Examples of substituents include a halogen, hydroxy, thiol, carboxy, methoxycarbonyl, hydroxymethyl, acetoxymethyl, cyano and acetylamino. Examples of the halogen is the same as those provided for AD. Preferably the ring is unsubstituted. _ ^ »* Faith W« - *? ! In the ketone derivative of the present invention represented by the formula [ID], XD is preferably S, O or SO, more preferably S. In YD in the ketone derivative represented by the general formula [ID], the aliphatic hydrocarbon group of Linear or branched chain having 1 to 6 carbon atoms include an alkyl or an alkenyl. Examples of the alkyl are methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl and tert-butyl. Examples of the alkenyl are vinyl, 2 -propenyl, isopropenyl and 2 -butenyl. Preferably the aliphatic group is an alkyl having 1 to 4 carbon atoms, more preferably ethyl. The aliphatic hydrocarbon group can be unsubstituted or substituted. When the aliphatic hydrocarbon group is substituted, the group may contain, for example, 1 to 6 preferably 1 to 4 substituents. As such substituents, this is carboxy or a group derived therefrom, amino or a group derived therefrom and hydroxy or a group derived therefrom. The aromatic hydrocarbon ring or aromatic heterocyclic ring • monocyclic having 3 to 6 carbon atoms refers to a An aromatic hydrocarbon ring such as a benzene ring and an aromatic heterocyclic ring such as a 5 or 6 membered ring containing nitrogen, oxygen or sulfur. Where the aromatic hydrocarbon ring or aromatic heterocyclic ring is substituted, for example such substituents is the same as those provided for the aliphatic hydrocarbon group. * 9? HSta & . > s? i & _ & & & - • ^ te-? 4 &TSÍ:.-r "siso"! The carboxy derivative group includes a carboxy functional group, such as an esterified or knotted carboxy group, cyano, hydroxymethyl or aminomethyl formed by reduction of these functional groups and functional groups derived therefrom by modification similar to acylation or alkylation of the functional groups Preferably, the carboxy and the group derived therefrom include carboxy, O0OR1 (wherein R1 is an unsubstituted alkyl or alkenyl) or substituted having 1 to 4 carbon atoms), 00NR2R3 (wherein each of R2 and R3, which may be different or the same and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 atoms carbon) and OOW (W is an unsubstituted or substituted heterocyclic ring.) Here the alkyl shown by Rl in C0OR1 may be linear, branched or cyclic Examples of the alkyl portion is methyl, ethyl, n-propyl, isopropyl, cyclopro pyl, n-butyl, isobutyl, tertbutyl and cyclobutyl, preferably methyl, ethyl and n-propyl, more preferably methyl. Examples of alkenyl are vinyl, 2-propenyl, isopropenyl and 2-butenyl. When the alkyl or alkenyl is substituted, for example, 1 to 6, preferably 1 to 3 substituents may be present. Exemplary of the substituents is a halogen, hydroxy, thiol, carboxy, methoxycarbonyl, acetyloxy, acetylthio, cyano and acetylamino. Example of the halogen is the same as defined for A. Preferably, the alkyl for R 1 is unsubstituted. Where the alkyl shown by R2 or R3 and the substituent is substituted, extents of such substituents are the same as those defined for Rl.

^^^^^^^^ ^^. Preferably, W represents a saturated heterocyclic ring, more preferably, an azetidine, piperidine, pyrrolidine, piperazine or morpholine ring. These hetercyclic rings can be carbonyl-coupled via carbon or nitrogen, preferably carbonyl via nitrogen. Where the heterocyclic ring is substituted from 1 to 4, preferably from 1 to 2 substituents may be present in each ring. Examples of the substituents are carboxy or a group derived therefrom and amino or a group derived therefrom. Examples of these substituents are as defined in the specification. Examples of the amino derivative group include such functional groups that the amino is alkylated, acylated or nitrosulfoylated, hydroxyamino, imino and a heterocyclic group containing the amino nitrogen atom, preferably a group shown by NR4R5 (wherein each of R4 and R5, which may be different or the same, independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms). In the group shown by NR4R5, the alkyl portion for R4 and R5 and substituents where the alkyl is substituted are the same as those defined for Rl. The acyl for R 4 and R 5 can be linear, branched, cyclic, saturated or unsaturated. Representative examples of the acyl are acetyl, propionyl, acroyl, propioloyl, n-butyryl, isobutyryl, crotonyl, valeryl, isovaleryl and pivaleyl. When the acyl is substituted, examples of the substituents are the same as those defined for Rl. Preferably, the amino group derived is NHQ0R14 (wherein R14 is an alkyl having from 1 to 4 carbon atoms in which the hydrogens can be substituted with fluorine; excerpts of the alkyl are the same as those provided for Rl). The number of fluorine atoms which may be substituted is 1 to 9, preferably 1 to 7. More preferably, R 14 is methyl. Exercises of the hydroxy derivative group include a functional group in which the hydroxy is alkylated or acylated, a keto and a halogen, preferably 0G0R15 (wherein R15 is an alkyl having from 1 to 4 carbon atoms and examples of the alkyl they are the same as those defined for Rl). ZD in the ketone derivative [ID] of the present invention represents carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a a group derived therefrom, sulfate or a group derived therefrom, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. Examples of the carboxy, amino or hydroxy derivative group are the same as defined above. Examples of the amino derivative group further include NHS02Ph, NHCDCF3, HOCjFs, HSGzC? ^ And HSC ^ Fs. The alkyl and alkenyl groups and the substituents wherein the alkyl or alkenyl is substituted are the same as those defined for A ^ Examples of the sulfate derivative group are sulfonamide derivative groups, for example, S02 H2, SQjNHCHj, S02N (CH3) 2 and SO2NHCOCH3. Examples of the phosphate derivative group are P (O) (OH) H, P (O) (OH) (NH,) and P (O) (OH) CH (OCH3) 2. Preferred Zen inclusions include carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be different or the same, independently represent hydrogen or a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms ), cyano, hydroxy, CH RIO (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms) NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represent hydrogen, a Unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, a halogen or hydrogen. Exercises of the alkyl portion shown by R7, R8, R9, RIO, Rll, R12 and R13 and substituents where the alkyl portion is substituted are the same as those defined for Rl.

Examples of the acyl shown by RIO, R12 and R13 and the substituents where the acyl is substituted is the same as those defined for R4.

A preferred combination for R12 and R13 is that R12 is hydrogen and R13 is ^ fc acetyl. Excipients of halogen are fluorine, chlorine, bromine and iodine, preferably fluorine and chlorine. More preferably examples of Zn are carboxy, COOR7 '(wherein R7 is an alkyl having 1 to 4 carbon atoms) and CH, OR10' (wherein RIO 'is hydrogen, an unsubstituted or substituted acyl having 1 to 5 carbon atoms ). Examples of R7 'are the same as those provided for Rl. Exercises of the acilo portion in RIO 'are the same as those provided for R4, plus Preferably, carboxy, methoxycarbonyl, hydroxymethyl and acetyloxymethyl.

[E] Compounds of formula [ÍE] The compound of formula [ÍE] is represented by formula [ÍE] above. [F] Compounds of formula 1F] 5 In the compounds of the present invention represented by the general formula [1F], the unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms, which is shown by i, it refers to an alkyl or alkenyl having 1 to 4 carbon atoms which may be optionally substituted. Exercises of the alkyl group are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. Examples of alkenyl are vinyl, 2-propenyl, isopropenyl and 2-butenyl. Preferably, the aliphatic hydrocarbon group is exemplified by methyl, ethyl, n-propyl and isopropyl, more preferably methyl. The aliphatic hydrocarbon group can be unsubstituted or substituted. When the group Aliphatic hydrocarbon is substituted, for example 1 to 6, preferably 1 to 3 substituents may be present. Examples of the substituents are an alkyl having 1 to 4 carbon atoms, halogen, hydroxy, an alkyloxy having 1 to 4 carbon atoms, amino, a monoalkylamino or a dialkylamino having 1 to 4 carbon atoms, Nitro, cyano, trifluoromethyl, carboxy, an alkyloxycarbonyl having from 1 to 4 carbon atoms, an acyloxy having from 1 to 5 carbon atoms, an acylthio having from 1 to 5 carbon atoms and an acylamino having from 1 to 5 carbon atoms. Examples of halogen are bromine, chlorine and fluorine. Excerpts of the alkyl having 1 to 4 carbon atoms and the KtfL -., Ar & - ...,, ^ ÍSIA '.liS ^ íkS:. ^. alkyl having 1 to 4 carbon atoms in the acyl having 1 to 5 carbon atoms are the same as those defined for Ap. The unsubstituted or substituted aromatic hydrocarbon ring group, aromatic heterocyclic ring or a saturated heterocyclic ring shown by Ap in the compounds of general formula [1F] include a ring of benzene, 1-naphthalene, 2-naphthalene, thiophene, furan, pyrrole, imidazole, oxazole, pyrazole, isoxazole, pyridine, pyrazine, indianoquinoline, isoquinoline, quinazoline, coumarin, pyrrolidine, piperidine or piperazine, preferably a benzene ring and a monocyclic aromatic heterocyclic ring, more preferably a benzene ring. These rings may be unsubstituted or substituted. When the ring is substituted, for example, 1 to 6, preferably 1 to 3 substituents may be present in each ring. Examples of the substituents include an alkyl having 1 to 4 carbon atoms, a halogen, hydroxy, an alkyloxy having 1 to 4 carbon atoms, amino, monoalauilarpine or dialkylamino having 1 to 4 carbon atoms, thiol , carboxy, an alkyloxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms, an acylamino having 1 to 5 carbon atoms cyano and trifluoromethyl. Examples of halogen are bromine, chlorine and fluorine. Examples of the alkyl having 1 to 4 carbon atoms and the alkyl portion in the acyl having 1 to 5 carbon atoms are the same as those provided for A. Preferred examples of Ap are those unsubstituted or those substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, a halogen or trifluoromethyl for 1 to 3 hydrogen atoms.

In the compounds of the general formula [1F], examples of the unsubstituted or substituted aliphatic hydrocarbon group Bp having 1 to 4 carbon atoms are the same as those provided for Ap. In the compound of the general formula [1F], Ap and Bp are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having from 3 to 7 carbon atoms. The ring spindles include a ring cyclopropan-1-one, cyclobutan-1-one, cyclopentan-1-one, cyclohexane-1-ina and cycloheptan-1-one, preferably a ring cyclobutan-1-one, cyclopentan-1 ina and cyclohexan-1-one, more preferably cyclopentan-1-one. These rings may be unsubstituted or substituted. When the ring is substituted, for example, one or two substituents may be present in each ring. Exercises of substituents include a halogen, hydroxy, carboxy, methoxycarbonyl, acetoxy, acetylthio, cyano and acetylamino. Examples of halogen are bromine, chlorine and fluorine. As an example that the two substituents exist, a ring fused with an aromatic hydrocarbon ring or an aromatic heterocyclic ring is representative. Examples of the aromatic hydrocarbon ring formed by Ap and Bp are an anolle benzene and a naphthalene ring. Examples of the aromatic heterocyclic ring are a 6-membered aromatic heterocyclic ring such as a pyridine, pyrazine or pyrimidine ring and a 5-membered heteroaryl such co-thiophenol, pyrrole, furan, oxazole, thiazole, isoxazole, isothiazole or azole ring. Preferably, the group formed by Ap and Bp is an aromatic hydrocarbon ring, more preferably a benzene ring. When the ring is substituted, the excerpts of the substituents are an alkyl having 1 to 4 carbon atoms, for example an unsubstituted alkyl such as ethyl, n-propyl and isopropyl, or an alkyl substituted with a halogen (for example fluorine). ) such as trifluoromethyl, an alkoxy having 1 to 4 carbon atoms such as methoxy and ethoxy; nitro and a halogen, for example fluoro, chloro or bromo. Specific examples are indan-1-one, 6,7-dihydro-5-oxocyclopenta [b] pyridine and 5,6-dihydro-7-oxocyclopenta [b] pyridine, preferably indan-1-one. In the compounds of the present invention represented by the general formula [1F], the straight or branched chain aliphatic hydrocarbon group having from 1 to 10 carbon atoms, which is shown by Xp or YF, referring to an alkyl or alkenyl which has 1 to 10 carbon atoms. Preferably, the aliphatic hydrocarbon group is an alkyl having from 1 to 6 carbon atoms and excerpts from the alkyl group are ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl and isobutyl, more preferably ethyl . The aliphatic group can be unsubstituted or substituted. Where the aliphatic group is substituted, the aliphatic group may contain, by way of example, from 1 to 6, preferably from 1 to 3 substituents. Examples of the substituents are carboxy or a group derived therefrom, amino or a group derived therefrom and hydroxy or a group derived therefrom.

The carboxy derivative group includes a carboxy functional group, such as an esterified or amidated carboxy group (eg, -C00R1, -OOORl ', -COOR ", -00NR2R3, -CDNR2'R3', O0NR2" R3", Etc. described below), cyano, hydroxymethyl, or aminomethyl formed by reducing these functional groups and functional groups derived therefrom by modification similar to acylation of functional groups (eg, -O ", 0R4, -CH20R4 ' down) . Examples of the amino derivative groups include such functional groups that the amino is alkylated, acylated or sulphonylated (for example 5-R6R7 described below), nitro, hydroxyamino, imino and a heterocyclic group containing the amino nitrogen atom. Examples of the hydroxy derivative group include a functional group in which the hydroxy is alkylated or acylated (eg, -0R5 described below), a keto and a halogen. In the compound of the present invention represented by the general formula [1F], examples of the heterocyclic group formed by the connection Xp and YF linked together directly or via a heteroatom are a ring of pyrrole, imidazole, indole, indazole, purine , carbazole, imidazolidine, imidazoline, pyrrolidine, piperidine, piperazine, morpholine and indoline.

Preferably, the heterocyclic group is a monocyclic heterocyclic ring such as pyrrole, imidazole, imidazolidine, imidazoline, pyrrolidine, piperidine, piperazine and morpholine, more preferably a saturated monocyclic heterocyclic ring such as a pyrrolidine, piperidine and morpholine. These rings may be unsubstituted or replaced. Where the ring is substituted, for example, 1 to 6 preferably 1 to 3 substituents may be present in each ring. Examples of the substituents include an alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom and hydroxy or a group derived therefrom. Ejepplos del The group derived from carboxy, amino or hydroxy are described above.

Preferred examples of the substituents are an alkyl having from 1 to 4 carbon atoms and phenyl, more preferably methyl and phenyl. Preferred examples of the substituted heteroaryl are imidazolidine and piperazine rings, more preferably a 4-methylpiperazine ring and 4-p-enylpiperazine ring. In the compounds of the present invention represented by the general formula [1F], ZF is carboxy or a group derived therefrom, an alkyl or alkenyl, substituted or unsubstituted, having 1 to 4 carbon atoms, hydroxy or a derivative group of the same, amino or a group derived therefrom, sulfate or a group derived therefrom, phosphate or a group derived therefrom, a monocyclic heteroaryl or a halogen. Examples of the carboxy, amino or hydroxy derivative group are described above. Examples of the amino derivative group further include NHS02Ph, NHC0CF3, NHCOC2F5M NHS02CF3 and NHS02C2F5. Examples of the sulfate derivative group are compounds from sulfonamide derivatives, for example S02NH2, S02NHCH3, S02N (CH3) 2 and S02NHCOCH3. Examples of the phosphate derivative group are P (O) (OH) H, P (O) (OH) (NH2) and P (O) (OH) CH (OCH3) 2. Examples of the alkyl group having 1 to 4 carbon atoms are methyl, ethyl, n-propyl, isopropyl and n-butyl. Examples of the alkenyl having 1 to 4 carbon atoms are vinyl, 2-propenyl, isopropenyl and 2-butenyl; when the alkyl or alkenyl is substituted, the examples of such substituents are the same as those defined for the aliphatic group in AF. Examples of monocyclic heteroaryl include 5-tetrazolyl, 3- (4H-5-oxo-1,2,4-oxadiazolyl), 5- (3-hydroxyisoxazolyl), 5- (3-hydroxyisothiazolyl) and 4- (3- hydroxy-l, 2,5-thiadiazolyl). Examples of halogen are fluorine, chlorine, bromine and iodine. The most preferred examples of ZF are carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or phenyl), with R2R3 (wherein each R2 and R3, which may be different or equal) , independently represent hydrogen or a substituted or unsubstituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), -OR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine and fluorine. Examples of the substituents for the alkyl or the acyl are the same as those defined for the substituents of the aliphatic group shown by AF. The most preferred examples of AF are carboxy, COOR1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein each of R2 'and R3', which may be different or the like, independently represent hydrogen or an alkyl having 1 to 4 carbon atoms), cyano and CH2OR4 '(wherein R4' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 atoms of carbon). ZF, as particularly preferred examples include carboxy, C00R1"(wherein R1" is methyl or ethyl), CONR2"R3" (wherein each of R2"and R3", which may be different or equal, independently represent hydrogen , methyl or ethyl) and cyano. Representative examples of the compounds according to the present invention are included below: Compounds of the formula [ÍA] (ÍA) trans-4- acid. { (2R) -2-acetylamino-2-carboxyethylthio} - methyl-3 -oxo-1-cyclopentanecarboxylic; 2A) trans-4- acid. { (2R) -2-acetylamino-2-methylcarbonyl-tylthio} methyl-3 -oxo-1-cyclopentanecarboxylic, • (3A) 2RS, 4S) -2-. { (2R) -2-acetylamino-2-carboxyethylthio} methyl-4-hydroxy-1-cyclopentanone; (4A) 2RS, 4S) -2- [(2R) -3-acetylamino-3 -. { 1- . { (2S) -2- toxycarbonyl Jpyrrolidinyl] -3-oxypropylthio} methyl-4-hydroxy-1-cyclopentanone; ? A) 2- acid. { (2R) -2-acetylamino-2-carboxyethylthio} methyl-3-oxo-1-indanecarboxylic; (6A) 2- acid. { (2R) -2-acetylamino-2-methoxycarbonylethylthio} methy1-3 -oxo-1-indanecarboxylic acid; Compounds of formula [IB] (IB) acid (1R, 2S) -2- [(2R) - [2 -acetylamino-3-oxo-3 - (1-pyrrolidinyl)} propylthio] methyl-3-oxo-l-cyclopentanecarboxylic; (2B) (lR, 2S) -2 - [(2R) - acid. { 2-Acetylamino-3- (4-morpholinyl) -3 -oxo} propyl thio] methyl-3 -oxo-1-cyclopentanecarboxylic acid; (3B) acid (IR, 2S) -2- [(2R) -. { 2-Acetylamino-3 -oxo-3- (1-piperidinyl) propylthio} ] met il -3-oxo-l-cyclopentanecarboxylic; (4B) acid (1 R, 2 S) -2 - [(2 R) - (. {2-carboxy-2-pentaf luoroprop-onylamino) -ethylthio] -methyl-3-oxo-1-cyclopentanecarboxylic acid; (5B) trans-2- [(2R) -. { 2-Acetylamino-3 -oxo-3 - (1-pyrrole idinyl)} propylthio] methyl-3-methoxycarbonyl-1-cyclopentanone; (6B) trans-2- [(2r) - [2-acetyl ami -3- acid. { 1- ((2S) -2-methoxycarbonylpyrrole idinyl)} -3 -oxo] propylthio] methyl-3-oxo-1-cyclopentanecarboxylic; ? B) trans acid 2 - [(2R) - [2-acetylamino- 3 -. { l- ((2S) -2- methoxycarbonylacet idinyl)} -3-oxo] propylthio] methyl-3-oxo-1-cyclopentanecarboxylic acid; (8B) trans-2- [(2R) - (2-carboxy-2-pentaf luoropropionylamino) -ethylthio] methyl-3-hydroxy-1-yl-cyclopentanone; : 9B; a c i do t ran s - 2 - [(11 - ac e t i l am i no - l l - c a r b o x i) unde c i l t i o] me t i l - 3 - ox o - 1 - cyclopentanecarboxylic; (10B) (1R, 2S) -2- [(2R) - (2-acetyl-ami-3 -oxo-3- (1-piperazinyl) propylthio}.] Met il-3 -oxo-1 acid - cyclopentanecarboxylic acid (11B) (lR, 2S) -2- [(2R) -. {2-acetylamino-3-oxo-3- (1- (4-hydroxymethyl) piperazinyl) propylthio}.] methyl- 3-oxo-1-cyclopentanecarboxylic acid (12B) (1R, 2S) -2- [(2R) -. {2-acetylamino-3-oxo-3- (1- (4-tert-butoxycarbonyl) piperazinyl)) propylthio.].] - methyl-3-oxo-1-cyclopentanecarboxylic acid; (13B) (lR, 2S) -2- [(2R) - [2-acetylamino-3 -oxo- 3 -. {l- ( 4- phenyl) piperazinyl [propylthio]] methyl-3-oxo-l-cyclopentanecarboxylic acid;? 4B) (1R, 2S) -2- acid. { 3- (3-pyridyl) propyl thio} methyl-3 -oxo-1-cyclopentanecarboxylic acid; (15B) acid (IR, 2S) -2- [3-. { 3- (1- Ipyridinyl iodide) } - propylthio] -methyl-3-oxo-1-cyclopentanecarboxylic acid (16B) acid (IR, 2S) -2- [2-acetylamino-2 - (5-tet ra zolyl) ethylthio]] methyl-3 - oxo-l-cyclopentanecarboxylic; Compound of formula [1C1 (C) 5 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-2-cyclopenten-1-one; (2C) (4R) -2 - [(2R) - (2-acetylamino-2-carboxy) ethylthio] methyl-4-hydroxy-2-cyclopenten-1-one; (3C) 2 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-3-hydroxy-2-cyclopenten-1-one; O 5- [(2R) - (2-acetylamino-2-carboxy) ethylthio] methyl-4-carboxy-2-cyclopenten-1-one; (5C) 5 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-methoxycarbonyl-2-cyclopenten-1-one; (6C) 5- [(2R) -2- (2 -acetylamino-2-carboxy) ethylthio] methyl-4-hydroxymethyl-2-cyclopenten-1-one; (7C) 5- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-acetoxymethyl-2-cyclopenten-1-one; (8C) 5- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylthio] methyl-4-carboxy-2-cyclopenten-1-one; (9C) 5- [(2-Acetylamino) ethylthio] methyl-4-carboxy-2-cyclopenten-1-one; (10 C) 2 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-3-carboxy-2-cyclopenten-1-one; : ??? or 2- [(2R) - (2-acetylamino-2-carboxy) ethylthio] methyl-3-methoxycarbonyl-2-cyclopenten-1-one; (12C) 2 - [(2R) - (2 -acetylamino-2-carboxy) ethylthio] methyl-3-hydroxymethyl-2-cyclopenten-1-one; (13C) 2- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-3-acetoxymethyl-2-cyclopenten-1-one; (14C) 2- [(2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthio] methyl-3-carboxy-2-cyclopenten-1-one; (15C) 2- [(2-methoxycarbonyl) ethylthio] methyl-3-ca-rboxi-2-cyclopenten-1-one; (16C) 2- [(2-Acetylamino) ethylthio] methyl-3-carboxy-2-cyclopenten-1-one.

Compounds of formula [ID] (ID) acid 3-. { (2R) -2-acetylamino-2-carboxyethylthio} methyl-4-oxo-1-n-pentanoic; (2D) 3- acid. { (2R) -2-acetylamino-2-methoxycarbonyl-ethylthio} methyl-4 -oxo-1-n-pentanoic; ! 3D) trans-2-. { (2R) -2-acetylamino-2-methoxycarbonylethylthio] -methyl-3-ethoxycarbonyl-1-cyclobutanone; (4D) trans-2- acid. { (2R) -2-acetylamino-2-carboxyethylthio} - methyl-3-oxo-1-cyclobutanecarboxylic, • (5D) 2- (2,3-dihydroxy-n-propyl) thiomethyl-3-acetoxymethyl-1-cyclobutanone; D) 2- acid. { (2R) -2-acetylamino-2-carboxyethylthio} methyl-3-oxo-l-cyclohexanecarboxylic; (7D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4-phenylbutyric acid; (8D) 3 - [(2R) - (2-Acetylamino-2-methoxycarbonyl) -ethylthio] methyl-4-oxo-4-phenylbutyric acid; (9D) 3 - [(2R) - (2-Acetylamino-2-methoxycarbonyl) -ethylthio] methyl-4- (4-methoxyphenyl) -4-oxobutyric acid; (10D) 3 - acid. { 2 - (acetylamino) ethylthio} met il -4- (4-methoxyphenyl) -4-oxobutyric; (11D) 3 - acid. { 2 - (acetylamino) ethylthio} methyl -4 -oxo-4-phenylbutyric; (12D) acid3-. { 2- (acetylamino) ethylthio} methyl-4- (4-methylphenyl) -3-oxobutyric; (13D) 3- acid. { (2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthio} - methyl-4- (4-methylphenyl) -3-oxobutyric; (14D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (4-trifluoromethylphenyl) butyric acid; (15D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (2-trifluoroethylphenyl) butyric acid; (16D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (3-trifluoromethylphenyl) butyric acid; (17D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (3-pyridyl) butyric acid; (18D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (2-pyridyl) butyric acid; (19D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (4-pyridyl) butyric acid; (20D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4- (1-naphthyl) -4-oxobutyric acid; (21D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4- (2-naphthyl) -4-oxobutyric acid; (22D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4-l-piperidyl) butyric acid; (23D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl -4- (4-methyl-1-p-perazinyl) -4-oxobutyric acid; (24D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (4-phenyl-1-piperazinyl) butyric acid; (25D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl -4- (2-furyl) -4-oxobutyric acid; (26D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4- (3-furyl) -4-oxobutyric acid; (27D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (2-thienyl) butyric acid; (28D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (3-t-enyl) butyric acid; (29D) 3- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (2-pyrrolyl) butyric acid; (30D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (3-pyrrolyl) butyric acid; (31D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4- (2-imidazolyl) -4-oxobutyric acid; (32D) 3 - [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-oxo-4- (3-pyridyl) butyric acid; (38D) 4 - [(2R) - acid. { (2-acetylamino-2-carboxy) ethylthio} ] methyl-5 -oxo-5-f-enylpentanoic acid; Compounds of formula [ÍE] (ÍE) acid (IR, 2S) -2 - [N- (pantoyl-alani-lamido) -ethylthio] methyl-3 -oxo-1-cyclopentanecarboxylic acid; Compounds of formula [1F] (1F) 4-Oxo-4-phenyl-3- (1-piperidyl) methylbutyric acid; (2F) 4- (4-methylphenyl) -4 -oxo-3- (1-piperidyl) -methylbutyric acid; (3F) 4- (4-methoxyphenyl) -4-OXO-3- (1-piperidyl) -methylbutyric acid; (4F) 4-oxo-4-f-enyl-3- (1-pyrrolidinyl) methylbutyric acid; (5F) 3- (4-morpholinyl) methyl-4-oxo-4-f-enylbutyric acid; (6F) 3 - acid. { 1- (4-methyl-piperazinyl)} met il-4 -oxo-4-f-enylbutyric; (7F) 3- (diethylamino) methyl-4-oxo-4-f-enylbutyric acid; Wfaidi (8F) acid (IR, 2R) -3-OXO-2- (1-piperidyl) methyl-1-cyclopentanecarboxylic acid; (9F) 4-Oxo-3- (1-piperidyl) methyl-4- (4-trifluoromethylphenyl) butyric acid; (10F) 4-OXO-3- (1-piperidyl) methyl-4- (2-trifluoromethylphenyl) butyric acid; (11F) 4-OXO-3- (1-piperidyl) methyl-4- (3-trifluoromethylphenyl) butyric acid; (12F) 4-Oxo-3- (1-piperidyl) methyl-4- (3-pyridyl) butyric acid; (13F) 4-Oxo-3- (1-piperidyl) methyl-4- (2-pyridyl) butyric acid; (14F) 4-Oxo-3- (1-piperidyl) methyl-4- (4-pyridyl) butyric acid; (15F) 3-Oxo-2- (1-piperidyl) methyl-1-indanecarboxylic acid; (16F) 3-Oxo-2- (1-pyrrolidinyl) methyl -1-indanecarboxylic acid; (17F) 2- (4-morpholinyl) methyl-3-oxo-l-indanecarboxylic acid; (18F) 2- acid. { 1- (4-methylpiperazinyl)} met il-3-oxo-1-indanecarboxylic acid; (19F) 3- acid. { 1- (4-phenylpiperazinyl)} met il -4 -oxo-4-phenylbutyric; (20F) 4-OXO-4- (1-naphthyl) -3- (1-piperidyl) methylbutyric acid; (21F) 4 -oxo-4- (2-naphthyl) -3- (1-piperidyl) methylbutyric acid; (22F) acid 4-OXO-4- (1-piperidyl) -3- (1-piperidyl) methylbutyric acid; (23F) 4-OXO-4- (4-methyl-l-piperazinyl) -3- (1-piperidyl) methylbutyric acid; £ Lje &2SS & S (24F) 4-oxo-4- (4-phenyl-1-piperazinyl) -3- (1-piperidyl) methylbutyric acid; (25F) a c i d o 4 - or x or - 4 - (l - n a f t i l) - 3 - (l - pyrrolidinyl) methylbutyric; (26F) á c i do 4 - or xo-4 - (2-n a f t i l) -3- (1-pyrrolidinyl) methylbutyric; (26F) 4- (2-furyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (27F) 4- (3-furyl) -4-oxo-3- (1-piperidyl) methylbutyric acid; (28F) 4-OXO-3- (1-piperidyl) methyl-4- (2-thienyl) butyric acid; (29F) 4-OXO-3- (1-piperidyl) methyl-4- (3-thienyl) butyric acid; (30F) 4-OXO-3- (1-piperidyl) methyl-4- (2-pyrrolyl) butyric acid; (31F) 4-Oxo-3- (1-piperidyl) methyl-4- (3-pyrrolyl) butyric acid; (32F) 4 - (2-imidazolyl) -4 -oxo-3- (1-piperidyl) methylbutyric acid; (33F) 4-oxo-4-phenyl-3- (1-piperidyl) methylbutyronitrile; (34F) Methyl 4-oxo-4-phenyl-3- (1-piperidyl) methylbutyrate; (35F) ethyl 4-oxo-4-phenyl-3- (1-p-peridyl) methylbutyrate; (36F) 4- (2-imidazol-yl) -4-oxo-3-81-pyrrolidinyl) -methyl-butyric acid; (37F) 4 -oxo-4-phenyl-3- (1-pyrrolidinyl) methylbutyronitrile; (38F) 4 - or x or - 4 - f e n i l -3- (4-m e t i l-l-piperazinyl) methylbutyronitrile; (39F) 4-oxo-4-phenyl-3- (4-morpholinyl) methylbutyronitrile; (40F) 4- (2-imidazolyl) -4-OXO-3- (4-morpholinyl) methylbutyric acid; (41F) 2-met i-l-4-oxo-4-phenyl-3 - (1-piperazinyl) methylbutyric acid; 5 (42F) 4- (1-piperazinyl) methyl-5-oxo-5-phenylpentanoic acid.

The compounds of the present invention may also be present in the form of stereoisomers such as geometric isomers and mixtures thereof, diastereoisomers and mixtures of them, optical isomers and racemic isomers. The compounds of the present invention cover all of these stereoisomers and mixtures thereof. The compounds of the present invention optionally may be in the form of pharmacologically acceptable salts of the same. Examples of such salts are salts with acids including inorganic salts such as hydrochlorides, sulfates, phosphates, and salts of group IIIA, for example aluminum salts, etc .; and organic salts such as p-toluenesulfonates. As salts with bases, there are salts with alkali metals such as sodium or potassium, salts with alkaline earth metals such as calcium, and organic salts with methylamine, ethylenediamine, etc. These pharmacologically acceptable salts of the compounds of the present invention can be Prepare by known methods.

The following are the representative processes for preparing the compounds of the present invention, but which are not considered limited to these processes only. The compounds of the present invention shown below and intermediates thereof can be isolated by conventional means of extraction, recrystallization, chromatography and the like.

[A] Process for producing compounds of formula fAA] Compounds of general formula [A], wherein XA is S, O or NH, are prepared by reacting cyclopentanone derivatives (the carbonyl at position 1 thereof can be protected if necessary, then simply referred to as derivatives reagents) represented by the general formula [2A]: OR C2A] 22? twenty-one? (where U is a leaving group and, Z1'A, Z2'A and Z3'A have the same meaning as defined in Z1A, Z2A and Z3A but when these groups contain functional groups, these groups may be optionally protected), with compounds of the general formula [3A]: HXA2 [3A] (where XA2 is S, 0 or NH and Y'A has the same meaning defined for YA, but when it contains a functional group, the functional group may be protected, if desired), and when required, remove the protective group . Preferred examples of the reactive derivatives described above are compounds of the general formulas [4A], [5A], [6A], [7A] and [8A]. [4A] C5A] HjH rft * t1r ^ - * áirt * ^ "* &108 [6 A] [7 A] In the, R15 is a hydrocarbon group having 1 to 10 carbon atoms, such as an [8A] alkyl, an alkenyl or an aryl. These groups can be 0 substituted or unsubstituted. When the substituents are functional groups, the functional groups may be protected with protecting groups, if necessary and so desired. Each of R16 and R17, which may be the same or different, independently represent an alkyl having 1 to 4 carbon atoms, or R16 and R17 combine together to form a piperazine or pyrrolidine ring. Z1'A, Z2'A and Z3'A have the same meaning as defined above. Examples of the compounds of the general formulas. { 4A], [5A], [6A] and [7A] are illustrated below. 0 (a) 4- [(2, 3-0-isopropylidene) propylsulfonyl] -methyl-3-oxo-1-cyclopentanecarboxylic acid; (b) 4-methylidene-3-oxo-1-cyclopentanecarboxylic acid; (c) (2RS, 4S) -2-. { (2R) - (2-Acetylamino-2-methoxycarbonyl) 5-ethylsulfonyl} methyl-4-hydroxycyclopentan-1 -one; ^ a ^^^^ m ^^^^ In the general formula [3A] wherein XA is S and YA is a residue derived from amino acid, the compounds of formula [3A] which include the following: (d) (2R) -2-acetylamino-2-carboxyethiaothiol (3) (2R) -2-acetylamino-2-methoxycarbonylethanethiol.

For this reaction, any condensation process can be used insofar as the compounds of formula [2A] can be condensed with the compounds of formula [3A]. The reaction is generally carried out in an organic solvent, water or a mixture thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc .; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc .; a halogenated hydrocarbon such as methylene chloride, chloroform, etc .; a ketone such as acetone, methyl ethyl ketone, etc .; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc. Preferred examples of the solvent are an ether such as tetrahydrofuran or diethyl ether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or methyl ethyl ketone, an aprotic polar solvent such as dimethyl sulfoxide or dimethylformamide, or a mixture of such solvent and water. The reaction generally proceeds in the presence of an acid or a base or in the absence of any catalyst, íi7T ¿£ gí 'tßto ü &?. preferably under basic conditions using inorganic bases, for example potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or organic bases such as triethylamine, etc. These reagents are used in an amount of about 0.1 to 20 times the moles, preferably 0.5 to 5 times the moles. The reaction temperature is not particularly limited so that the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between 0 ° C and 100 ° C. The compounds of formula [2A] can be reacted with the compounds of formula [3A] in an equimolar amount. Practically, the compounds of formula [3A] can be used in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 200 hours, preferably 0.1 to 72 hours. Compounds of formula [IA] wherein XA is S02 can be prepared by oxidizing the compounds of formula [IA] wherein XA is S, with an oxidizing agent. As the oxidizing agent can be used to m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as permanganate, chromic acid, ruthene tetroxide, etc., hydrogen peroxide, an organic peroxide, etc., preferably an organic peracid such as m-chloroperbenzoic acid.

Compounds of formula [IA] wherein XA is SO can be prepared by oxidizing compounds of formula [IA] wherein XA is S, with an oxidizing agent. As the oxidizing agent, an organic peracid such as m-chloroperbenzoic acid, etc., can be used, an inorganic oxidizing agent such as manganese dioxide, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, an halogen-type oxidizing agent such as periodic acid, etc. For example, the compounds (a) and (b) described above are prepared by the following procedure. (1A-Q (1 A-c) «sßUS? - Starting with 2,4-bis (methoxycarbonyl) cyclopentanone (compound 1A-A) which is known and can be prepared as a mixture of 2,3-bis (methoxycarbonyl) cyclopentanone (Compound IA-a) by the process described, for example, in J. Org. Chem., 47, 2379 (1982) or by a modification thereof. After the keto group is protected from the mixture (compound 1A-B and compound lA-b), the ester is converted to hydroxymethyl by reduction.

The protecting group is then removed to provide 2,4-bis (hydroxymethyl) cyclopentanone (compound 1A-C) and 2,3-bis (hydroxymethyl) cyclopentanone (compound 1A-c). The compound (lA-c) is removed by column chromatography on silica gel to isolate the compound (1A-C). The compound (1A-C) is acetylated in a conventional manner to provide the compound (1A-D). The reaction for preparing the compound (1A-E) from the compound (1A-D) is carried out under conditions similar to those used for the condensation between the compounds of the formula [2A] and the compounds of the formula [3A] . In this case, alpha-thioglycerin is used as the compound of formula [3A]. Then, the 1,2-diol portion in the compound (1A-3) is protected. As the protecting group, a ketal, a ketal or an orthoester may be used. The compound (1A-E) is then converted to the isopropylidene preferably in the presence of an acid catalyst and acetone or its activated derivatives to provide the compound (1A-F). Subsequently, the compound (1A-F) is subjected to alkaline hydrolysis in a conventional manner to remove the acetyl and provide the compound (1A-G). Then, the sulfide of the compound [1A-G] is oxidized to form the sulfone. Therefore, compound [1A-H] is obtained. The reaction is carried out under conditions similar to those used for the preceding oxidation, wherein the conditions are set so as not to oxidize the hydroxy. In case the hydroxy is also oxidized, compound (a) is obtained. Then, the hydroxy is oxidized to provide the compound (a).

Examples of the oxidizing agent that can be used are inorganic oxidizing agents such as permanganates and chromic acid, preferably chromic acid. The compound (b) can be prepared by keeping the compound (a) under basic conditions similar to the conditions used for the condensation between the compounds of formula [2A] and the compounds of formula [3A]. In this reaction there is no need to add the compounds of formula [3A]. The reactants used for the reaction are inorganic bases, for example potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, etc., or bases Organic compounds such as triethylamine, 1,8-diazabicyclo [5.4.0] -undeca-7-ene, etc., preferably an organic base such as triethylamine. The compound (c) can be prepared by the following procedure. 25 fcLSte * gtti b | te É? iíágm The initial (4R) -2- (N, N-diethylamino) methyl-4-tert-butyldimethylsiloxy-2-cyclopenten-l-one (compound 3A-a) is known and commercially available (e.g., The Shin-Etsu Chemical Co., Ltd.). For the reaction to prepare the compound (3A-b) from the compound (3A-a), the reaction conditions similar to those used for the condensation between the compounds of the formula [2A] and the formula [3A] can be used. In this reaction N-acetyl-L-cysteine is used as the compound of formula [3B]. The protecting group for the hydroxy of the compound (3B-b) is removed in a conventional manner, using an acid or a fluorine compound. By oxidation, the sulfide of the compound (3B-c) is then gj ^. convert to the corresponding sulfone to provide the compound (3B-d). The reaction can be carried out under conditions similar to those for the above oxidation, so that they do not oxidize the hydroxy. The double bond in the ring is then reduced with a reducing agent to provide the compound (c). As the reducing agent, a catalytic reducing agent such as palladium-carbon, etc., a soluble metal reducing agent such as lithium-ammonia, etc., an organic tin hydride compound, an organic silicon hydride compound can be used. , etc., preferably a catalytic reducing agent such as palladium-carbon. The compounds of the general formulas [4A] to [7A] other than the compounds (a) to (c) described above can be prepared by appropriately modifying the above process used to prepare the compounds (a) to (c). Compound (c) is commercially available (for example from Tokyo Kasei K.K.). The compound (e) is easily prepared by heating the compound (d) in methanol in the presence of an acid catalyst. As the acid catalyst, there is an organic acid such as hydrochloric acid, sulfuric acid, etc., an organic acid such as p-toluenesulfonic acid or a Lewis acid such as boron fluoride etherate, etc., preferably an organic acid such as p-toluenesulfonic acid.

For example, the compound (4A) of the present invention can be easily prepared by amidation of the compound (3A) as shown below.

The amidation is carried out by condensation under basic conditions or by using a condensing agent. The use of a condensing agent is preferable for amidation. Examples of the condensing agent are dicyclocarbodiimide (DCC) and WSC. The compounds (5A) and (6A) of the present invention can be prepared by reacting the compounds of the general formula [8a] with the compounds of the general formula [3A] while heating. The reaction is carried out in the absence of a solvent or in an organic solvent with heating from 30 ° C to 230 ° C to provide the desired product. As the compounds of formula [8A], for example, (f) is 2- (1-piperidylmethyl) -3-oxo-l-indanecarboxylic acid representative. The compound (f) can be prepared by a modification of the process described in J. Med. Chem., 7, 716 (1964). || j ^^ tíjg U [B] Process for preparing the compounds of formula [1B1 Compounds of the general formula [IB] wherein XB is S, O or NH are prepared by reacting 2, 3-substituted cyclopentanone derivatives (the carbonyl at position 1 may be suitably protected, subsequently referred to simply as the reactive derivatives) represented by the general formula [2B]: (where U is a leaving group and Z'B has the same meaning as that of ZB, but when the group contains a functional group, the functional group may be adequately protected), with compounds of the general formula [3B]: HXB2 [3B] (where XB2 is S, O or NH and Y'B has the same meaning defined for YB, but when it contains a functional group, the functional group may be adequately protected), and when required, remove the protecting group. Preferred examples of the reactive derivatives described above are compounds of the general formulas [4B], [5B], [6B] and [7B].

C 6 B] [7 B] In the above formulas, R18 is an aliphatic group having 1 to 10 carbon atoms, such as an alkyl, an alkenyl or an aryl. These groups may be substituted or unsubstituted. When one or more functional groups are contained as a substituent or substituents, the functional groups may be suitably protected with protecting groups. Examples of the compounds of the general formulas [4B], [5B], [6B] and [7B] are given below. tftéwfc tt ^ aia (a) 2, 3-bis (acetoxymethyl) cyclopentanone (b) 3 -acetoxymethyl-2-methylidenecyclopentanone (c) 2- [(2,3-isopropylidene) propylsulfonyl] -methyl-3-oxo acid - 1-cyclopentanecarboxylic acid 5 (d) 2 - [(2,3-o-isopropylidene) propylsulfonyl] -met-il-3-methoxycarbonylcyclopentanone (e) 2-methylidene-3-oxo-l-cyclopentanecarboxylic acid (f) 3-methoxycarbonyl -2-methylidene cyclopentanone.

In the general formula [3B] wherein XB is S and YB is a residue derived from amino acid, the compounds of formula [3B] include the following: (g) (2R) -2-acetylamino-3-oxo-3- (1-pyrrolidinyl) propanothiol 15 (h) (2R) -2-acetylamino-3- (4-morpholinyl) -3-oxo-propanethiol (i) (2R) -2-acetylamino-3-oxo-3- (1-piperidyl) propanothiol (j) (2R) -2-acetylamino-3-oxo-3- (1-pyrrolidinyl) propanothiol (k) ( 2R) -2-acetylamino-3- [l-. { (2S) -2-methoxycarbonyl} pyrrolidinyl) -3-oxopropanothiol 20 (1) (2R) -2-acetylamino-3 - [1-. { (2S) -2-methoxycarbonyl} acetidinyl) -3-oxopropanethiol (m) (2R) -2-acetylamino-3-oxo-3- (1-piperazinyl) propanethiol (n) (2R) -2-acetylamino-3-. { 1- (4-Hydroxymethyl) piperazinyl} -3- oxopropanothiol (o) (2R) -2-acetylamino-3 -. { 1- (4-tert-butoxycarbonyl) piperazinyl) -3-oxo-propanethiol (P) (2R) -2-acetylamino-3-. { 1- (4-phenyl) piperazinyl} -3 oxopropanothiol (q) (2R) -2-carboxy-2-pentafluoropropionylaminoethanethiol (r) 1-acetylamino-1-carboxy-11-mercaptoundecanethiol (s) 2-acetylamino-2- (5-tetrazolyl) ethanethiol (t) 3 - (3-pyridyl) propanethiol (u) 3-. { 3- (1-methylpyridinium iodide) propanethiol The above reaction can be carried out through any condensation in that the extent to which the compounds of formula [2B] can be condensed with the compounds of formula [3B]. The reaction is generally carried out in an organic solvent, water or a mixture thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc; a halogenated hydrocarbon such as methylene chloride, chloroform, etc; a ketone such as acetone, methyl ethyl ketone, etc; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc. Preferred examples of the solvent are an ether such as tetrahydrofuran or diethylether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or methyl ethyl ketone, a polar aprotic solvent & Figure US08178153-20090212-C00003 EMI9.0 EMI3.0 EMI3.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4.0 EMI4 The reaction proceeds generally in the presence of an acid or a base or in the absence of a catalyst, preferably under basic conditions. The reactants used for the reaction are inorganic bases, for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or organic bases such as triethylamine 1,8-diazabicyclo [5.4. 0] -undeca-7-ene, etc. These reagents are used in an amount of about 0.1 to 20 times the moles, preferably about 0.5 to 5 times the moles. The reaction temperature is not particularly limited so that the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between 0 ° C and 100 ° C. The compounds of formula [2B] can be reacted with the compounds of formula [3B] in an equimolar amount. Practically, the compounds of formula [3B] can be used in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 200 hours, preferably 0.1 to 72 hours. The compounds of formula [IB] wherein XB is S02 can be prepared by oxidizing the compounds of formula [IB] wherein XB is S, with an oxidizing agent. As the oxidizing agent there can be mentioned an organic peracid such as m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as permanganate, acid - ^ - S ^ & ^ ^ - * H ^^ ZL ^ "^ ^^ ^ Z7 ^ - * - ^^ ~ - £ arí ^ £ £ teS? £ = ^ &SSS &F- Chloride, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, etc., preferably an organic peracid such as m-chloroperbenzoic acid The compounds of formula [IB] wherein XB is SO , can be prepared by oxidizing the compounds of formula [IB] wherein XB is S, with an oxidizing agent, As the oxidizing agent can be mentioned an organic peracid such as m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as manganese dioxide, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, a halogen-type oxidizing agent such as periodic acid, etc. For example, the compounds (a) and (b) described above they are prepared by the following procedure. (a-1) (a) (b) The initial 2,3-bis (hydroxymethyl) cyclopentanone (compound a-1) is known from the literature and can be prepared, for example, by the method described in Japanese Patent KOKAI No. Hei 5-1044 or a modification of the same The compound (a-1) is acetylated in a conventional manner to provide the compound (a). Compound (a) which is optically active and has a steric configuration of (2R, 3R) can be obtained according to the process described in Japanese Patent KOKAI No. Hei 8-231469. The optically active form of the compound (a) can also be prepared, for example by optical resolution of the optically inactive form by chromatography for optical resolution. Compound (b) can be prepared by keeping the compound (a) under basic conditions similar to the conditions used for the condensation between the compounds of formula [2B] and the compounds of formula [3B]; in carrying out this reaction, the compounds of formula [3B] need not be used. The reagents used for the reaction are inorganic bases, for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or organic bases such as triethylamine, 1,8-diazabicyclo [5.4 .0] -undeca-7-ene, etc., preferably an organic base such as triethylamine. The compounds (c) and (d) can be prepared as indicated below.

The reaction for preparing the compound (a-2) from the compound (a) is carried out under conditions similar to those used for the condensation between the compounds of the formula [2B] and the compounds of the formula [3B]. In this case, alpha-thioglycerin is used as the compound of the formula [3B]. Then, the 1,2-diol portion in the compound (a-2) is protected. As the protecting group, an acetal, a ketal or an ortho ester may be used. The compound (a-2) is then converted to the isopropylidene preferably in the presence of an acid catalyst and acetone or its activated derivatives to provide the compound (a-3). Subsequently, the compound (a-3) is subjected to alkaline hydrolysis in a conventional manner to remove the acetyl. Therefore, compound (a-4) is obtained. Then, the sulfide of the compound (a-4) is oxidized to the sulfone to prepare the compound (a-5). The reaction is carried out under conditions similar to those used for the oxidation described above wherein the conditions are those set so that the hydroxy is not oxidized. In the case where the hydroxy also oxidizes, compound (a) is obtained. The hydroxy is then oxidized to provide the compound (c). Examples of the oxidizing agent that can be used in the reaction are inorganic oxidizing agents such as permanganates and chromic acid, preferably chromic acid. Finally, the carboxylic acid in the compound (c) is esterified in a conventional manner to prepare the compound (d). The compounds (e) and (f) can be prepared from the compounds (c) and (d) under conditions similar to the conditions used to convert the compound (a) to the compound (b). The optically active form (compound C and D) of the compounds (c) and (d) can be prepared in a manner similar to the process for preparing the compounds (c) and (d) described above, which are illustrated below. fifteen The compounds of the general formulas [4B] to [7B] other than the compounds (a) to (f) described above can be prepared by appropriately modifying the above processes used to prepare the compounds (a) to (f). The compounds (g) to (u) can be prepared as shown below.

^^^^^^^ M ^^^! < ii% jjt¡-r. i ^ tiAffi ^ SBÉ? ttift (g-i) (£ -2) (g-3) (SHP) Benzoyl N-acetyl-L-cysteine (g-1) was prepared in a conventional manner to prepare the compound (g-2). Next, the compounds of general formula [8b] below: HW4 [8B] wherein W4 is 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 1- (2-methoxycarbonyl) azetidinyl, 1- (2-methoxycarbonyl) pyrrolidinyl, 1-p ipe razini 1 or, 1 - (4-hydroxyeti 1) piperazine 1 or, 3-phenylpiperazinyl or 1- (4-tert-butoxycarbonyl) piperazinyl are subjected to an amide-forming reaction in a conventional manner. Therefore, the compound (g-3) is prepared. The protective benzoyl is removed by hydrolysis to provide compounds (g) to (p).

The compound (q) can be easily prepared by reacting L-cysteine with pentafluoropropionic anhydride. The compound (r) can be prepared as shown below.

The compound (r-2) can be prepared by reacting the readily available compound (r-1) with diethyl acetylaminomalonate in the presence of a base, which is conventional for preparing amino acid derivatives. The protecting benzyl is then removed in a conventional manner to convert the compound (r-2) to the compound (r-3). The compound (r-3) is heated to decarboxylate under acidic conditions to prepare the compound (r-4). After the carboxy is protected in the form of methyl ester, the hydroxy is converted to acetylthio under moderate conditions in a conventional manner, using as reagents 2-fluoro-1-methylpyridinium p-toluenesulfonate, thiacetic acid and triethylamine. Therefore, the compound (r-5) is prepared. By removing methoxy and the S-acetyl protecting groups under mild basic conditions, compound (r) of the compound (r-5) is obtained. The compound (s) can be easily prepared by the processes which comprise converting COOH from the L-cysteine protected with thiol, cyano, to react with sodium azide to convert to 5-tetrazolyl and remove the protecting group to release thiol. Compound (t) can be easily prepared by the process described in Chemistry Letters, 133-136 (1977), using 3-pyridinepropanol as the starting compound. The compound (u) can be easily prepared by reacting the thiol-protected compound (t) with methyl iodide and then releasing the thiol by removal of the protecting group from the resulting pyridinium iodide.

[C] Processes for preparing the compounds of formula [1C1 Compounds of the general formula [ÍC] wherein Xc is S, 0 or NH are prepared by reacting cyclopentenone derivatives (the carbonyl at position 1 may be adequately protected, hereinafter referred to simply as the reactive derivatives) represented by the formula general [2C]: (where U is a leaving group and Zl'c, Z2'cy and Z3 'c have the same meaning as defined in Zlc, Z2C and Z3C but when the group contains a functional group, the functional group may be adequately protected), with compounds of general formula [3C]: HXC2 [3C] (where Xc2 is S, O or NH and Y'c has the same meaning as defined for Yc but when it contains a functional group, the functional group may be appropriately protected), and when required, remove the protecting group. Preferred examples of the reactive derivatives described above are compounds of the general formulas [4C], [5C], [6C],] 7C] and [8C].

S hffffled to C4C] C5c] C6c] C7C] C8c] In the above formulas, R16 is an aliphatic hydrocarbon group having 1 to 10 carbon atoms such as an alkyl, an alkenyl or an aryl. These groups may be substituted or unsubstituted. When a substituent or substituents are functional groups, the functional groups may be protected with protecting groups, if necessary and desired. Each of R17 and R18 represents hydrogen or an aliphatic hydrocarbon group having 1 to 10 carbon atoms, for example an alkyl, an alkenyl or an aryl. These groups may be substituted or unsubstituted. When the substituents are functional groups, the functional groups may be protected with protecting groups, if necessary and desired. Al'c, Z2'c and Z3'c have the same meaning as defined above. Examples of the compounds of the general formulas [4C], [5C], [6C],] 7C] and [8C] are illustrated below. (a) 2- [(2R) - (2-Acetylamino-2-methoxycarbonyl) -ethylsulfonyl] methyl-4-tert-butyldimethylsiloxy-2-cyclopentan-1-one (b) 2 -methylidene-4-tert-but ildime useful if loxy-2-cyclopentan-1-one 15 (c) 2-diethylaminomethyl-4-tert-butyldimethylsiloxy-2-c-clopenten-1-one (d) 3 -acetoxy-2-benzenesulfonylmethyl- 2 -cyclopenten-l-one.

In general formula [3C] wherein Xc is S, the 20 compounds of formula [3C] include the following: (e) (2R) -2-acetylamino-2-carboxyethanethiol (f) (2R) -2-acetylamino-2-methoxycarbonylethanethiol In order to carry out the above reaction, any process of condensation can be used to the extent that the compounds of formula [2C] can be condensed with the compounds of formula []. 3C]. The reaction is generally carried out in an organic solvent, water or mixtures thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc .; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc .; a halogenated hydrocarbon such as methylene chloride, chloroform, etc .; a ketone such as acetone, methyl ethyl ketone, etc .; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc. Preferred examples of the solvent are an ether such as tetrahydrofuran or diethylether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or methyl ethyl ketone, an aprotic polar solvent such as dimethyl sulfoxide or dimethylformamide, or a mixture of such solvent and water. The reaction proceeds generally in the presence of an acid or a base or in the absence of a catalyst, preferably under basic conditions using inorganic bases, for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or organic bases such as triethylamine, 1,8-diazabicyclo [5.4.0] -undeca-7-ene, etc. These reagents are used in an amount of about 0.1 to 20 times the moles, preferably about 0.5 to 5 times the moles. The reaction temperature is not particularly limited so that the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between 0 ° C and 100 ° C. The compounds of formula [2C] can be reacted with the compounds of formula [3C] in an equimolar amount. Practically, the compounds of formula [3C] are can use in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 200 hours, preferably 0.1 to 72 hours. When the compound (a) or the compound (b) are selected as the compounds of the formula [2C] the product of The resulting condensation is further dehydrated after removal of the protective group for the hydroxy, in order to provide the desired cyclopentenone derivative. As the reagents for removal of the protective group and dehydration, an acid, an acid resin, a Lewis acid or a fluorine reagent. The acid that can be used includes an inorganic acid such as hydrochloric acid or sulfuric acid and an organic acid such as p-toluenesulfonic acid and acetic acid. As the acid resin, Dowex 50 is preferred. The boron fluoride etherate or the like is advantageously used as the Lewis acid. The reagent The fluoride includes tetrabutylammonium fluoride and hydrogen fluoride in the compounds of general formula [2C] wherein Xc is N, that is, wherein the compounds of formula [7C] are condensed with the compounds of formula [3C], the objective condensation product can be prepared by methylating or oxidizing the nitrogen of the compounds shown by the formula [7C] and then reacting the methylated or oxidized product with the compounds of formula [3C] Examples of the methylating agent are methyl halide and dimethyl sulfate, preferably methyl iodide The oxidizing agent includes an organic peracid such as m-chloroperbenzoic acid, hydrogen peroxide, an organic peroxide, etc., preferably an organic peracid such as m-chloroperbenzoic acid or hydrogen peroxide The compounds of formula [ÍC] wherein Xc is S02 can be prepared by oxidizing the compounds of formula [IC] wherein Xc is S. oxidizing people suitable for use include an organic peracid such as m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as manganese dioxide, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, preferably an organic peracid such as acid, -chloroperbenzoic acid. Compounds of formula [IC] wherein X c is SO can be prepared by oxidizing the compounds of formula [C] wherein X c is S. The oxidizing agent suitable for use includes an organic peracid such as m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as manganese dioxide, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, an agent halogen type oxidant such as periodic acid, etc. For example, the compound (a) and the compound (b) described above can be prepared as follows: (C) (a-1) (a-2) (a) The starting compound (c) is known and commercially available, for example, from Nissan Chemical CO. , Ltd. Compound (c) can be converted to compound (a-1) under reaction conditions similar to those used for the condensation of compounds of formula [2C], wherein Xc is N. The following compound (a -2) can be produced under reaction conditions similar to those for the oxidation to S02 described above. The carbon-carbon double bond of the compound (a-2) is ** &- "- * s" can be reduced in a conventional manner to provide the compound (a) As the reducing agent can be used an alkaline metal reducing agent, an organic tin reducing agent, a reducing agent of organic silicon, a catalytic hydrogenation reducing agent, etc., preferably a catalytic hydrogenation reducing agent such as palladium-carbon, etc. Compound (b) can be prepared by keeping the compound (a) under basic conditions. which can be used for the basic conditions are an inorganic base such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., and an organic base such as triethylamine 1,8-diazabicy? clo [5.4.0] -undeca-7-ene, etc., preferably an organic base such as triethylamine or 1,8-d? azabicyclo [5.4.0] -undeca-7-ene. to 4S2zU.ZZ .'- jjt.¡A? a ^ Uj¿ZSfc ..; The compound (d-1) is known from the literature and can be prepared, for example, by the method described in J. Org.

Chem., 58, 3953-3959 (1993). By acetylation of the compound (d-1) In a conventional manner, compound (d) can be prepared. Compounds of the formula [4C] to [8C] other than the compounds (a) to (d) can be prepared by appropriately modifying the above processes to prepare the compounds (a) to (d). The compound (e) is commercially available, for example from Tokyo Kasei K.K. The compound (f) is easily prepared by heating the compound (e) in methanol, in the presence of an acid catalyst. As the acid catalyst, there are the organic acids such as hydrochloric acid, sulfuric acid, etc., an organic acid such as p-toluenesulfonic acid or a Lewis acid such as boron fluoride etherate, etc., preferably an organic acid such as p-toluenesulfonic acid.

[D] Process for preparing the compounds of formula [ID] Compounds of general formula [ID] wherein XD is S, O or NH are prepared by reacting ketone derivatives (in carbonyl at position 1 it may be appropriately protected; hereinafter referred to simply as the reactive derivatives) represented by the general formula [2D]: • (where U is a separating group, and A'D, B'D and Z'D have the same meaning as defined in AD, BD and ZD, but when the group contains a functional group, the functional group can be adequately protected) , with compounds of the general formula [3D]: HXD2 [ED] 15 (where XD2 is S, O or NH, and Y'D has the same meaning as defined for YD but when it contains a functional group, the functional group may be appropriately protected), and when required, remove the protective group. Preferred examples of the reactive derivatives described above are compounds of the general formulas [4D], [5D], [6D], [7D] and [8D].

C4 D] C 5 D] C 6 D] C7 D] C 8 D] In the above formulas, R16 is an aliphatic group having 1 to 10 carbon atoms, such as an alkyl, an alkenyl or an aryl. These groups may be substituted or unsubstituted. When a substituent or substituents are functional groups, the functional groups may be appropriately protected with protecting groups. Each of R17 and R18, which may be the same or different, independently represent an alkyl having 1 to 8 carbon atoms or R17 and R18 combine together to form a piperazine ring or a pyrrolidine ring. A'D, B'D and Z'D have the same meaning as defined above. R16 and Z'D can also be combined together to form a? -butyrolactone ring.

Examples of the compounds of the general formulas [4D], [5D], [6D], [7D] and [8D] are shown below. (a) 4-acetyl-β-butyrolactone (b) 3-methylidene-4-oxo-1-n-pentanoic acid (c) trans -2, 3-bis (acetoxymethyl) -1-cyclobutanone (d) 3 -acetoxymethyl -2-methylidene-1-cyclobutanone (e) 3-ethoxycarbonyl-2-methanesulfoxymethyl-1-cyclobutanone (f) 3-ethoxycarbonyl-2-methylidene-1-cyclobutanone (g) 2- [(2, 3-0- isopropylidene) propylsulfonyl] -methyl-3-oxo-1-cyclohexanecarboxylic acid (h) 2-methylidene-3-oxo-1-cyclohexanecarboxylic acid (i) 4-oxo-4-phenyl-3- (1-piperidyl) methylbutyric acid (j) 4-OXO-4- (3-pyridyl) -3- (1-piperidyl) methylbutyric acid (P) 4- (1-piperidyl) methyl-5-oxo-5-phenylpentanoic acid In the compounds of formula [3D] wherein XD is S, the compounds of formula [3D] include the following: (q) (2R) -2-acetylamino-2-carboxyethanethiol (r) (2R) -2-acetylamino-2-methoxycarbonylethanethiol (s) 2,3-dihydroxypropan-1-thiol (alpha-thioglycerin).

To carry out the above reaction, any condensation process can be used in that the extent that the compounds of formula [2D] can be condensed with the compounds of formula [3D]. The reaction is carried out in an organic solvent, water or a mixture thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc .; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc .; a halogenated hydrocarbon such as methylene chloride, chloroform, etc .; a ketone such as acetone, methyl ethyl ketone, etc .; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc. Preferred examples of the solvent to be used are an ether such as tetrahydrofuran or diethylether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or methyl ethyl ketone, an aprotic polar solvent such as dimethyl sulfoxide or dimethylformamide, an alcohol such as methanol or ethanol, or a mixture of such solvent and water. The reaction proceeds generally in the presence of an acid or a base or in the absence of a catalyst, preferably under basic conditions. When no catalyst is used, the reaction sometimes proceeds with heating. The reagents used to make the reaction system are an inorganic base such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or organic bases such as triethylamine, 1,8-diazabicyclo [5.4.0] -undeca-7-eno, etc. These reagents are used in an amount of about 0.1 to 20 times the moles, preferably about 0.5 to 5 times the moles. The reaction temperature is not particularly limited so that the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between -20 ° C and 130 ° C. When the condensation is carried out in the absence of a catalyst, the temperature is preferably between 30 ° C and 200 ° C. The compounds of formula [2D] can be reacted with the compounds of formula [3D] in an equimolar amount. Practically, the compounds of formula [3D] can be used in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 200 hours, preferably 0.1 to 72 hours. The compounds of formula [ID] wherein XD is S02 can be prepared by oxidizing the compounds of formula [ID] wherein XD is S. The oxidizing agent suitable for use in oxidation includes an organic peracid such as m-chloroperbenzoic acid, etc., an inorganic oxidizing agent such as permanganate, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, etc., preferably an organic peracid such as m-chloroperbenzoic acid. The compounds of formula [ID] wherein XD is SO can be prepared by oxidizing the compounds of the formula [ID] in where XD is S. The oxidizing agent suitable for use in oxidation includes an organic peracid such as m-chloroperbenzoic acid, an inorganic oxidizing agent such as manganese dioxide, chromic acid, ruthenium tetroxide, etc., hydrogen peroxide, an organic peroxide, a halogen-type oxidizing agent such as periodic acid, etc. For example, compound (a) and compound (b) described above can be prepared as follows. fifteen The compound (a) is known and can be prepared, for example, by the method described in Bull. Chem. Soc. Jpn., 32, 1282 (1959). The compound (b) is also known and can be prepare, for example, by the process described in the Japanese patent KOKOKU Showa 37-5911. Compound (b) can be prepared by keeping the compound (a) under acidic or basic conditions. The reagents used for the above reaction are one such as potassium hydroxide, sodium hydroxide, carbonate potassium, sodium carbonate, sodium hydride, etc., a base ^ as. ^. organic such as triethylamine 1,8-diazabicyclo [5.4.0] -undeca-7- ene, etc., an inorganic acid such as hydrochloric acid, sulfuric acid, etc., and an organic acid such as p-toluenesulfonic acid, preferably an organic base such as 5-triethylamine, 1,8-diazabicyclo [5.4.0] -undeca-7-ene or an inorganic acid such as sulfuric acid. The compounds (c) and (d) can be prepared as follows. (c) () fifteen The analogs of the compound (c) are known and described, for example, in Tetrahedron Lett., 6453 (1989) and the compound (c) itself can be easily prepared by the process described herein. The compound (d) can be prepared by keeping the compound (c) under basic conditions. The reagents that can be used advantageously for the reaction are an inorganic base such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, Sodium hydride, etc., and an organic base such as triethylamine This is a 1, 8-diazabicyclo [5.4.0] -undeca-7-ene, etc., preferably an organic base such as triethylamine or 1,8-diazabicyclo [5.4.0] -undeca-7-ene. The compounds (e) and (f) can be prepared as follows.

The compound (e-1) is known and can be prepared, for example, by the process described in J. Org. Chem., 53, 3841 (1988). To convert the compound (e-1) into the compound (e) and then the compound (f), the process described in J. is applied.

Org. Chem., 53, 611 (1988) by appropriate modification. This is, If the compound (e-2) can be prepared by treating the compound (e-1) with a base and treating the anions generated with formaldehyde, the base can be used as an LDA. , n-butyllithium, KHMDS, sodium hydride, etc., preferably LDA The formaldehyde is preferably reacted as a monomer after cracking its polymer Compound (e) can be prepared by mesylation of the compound (e-2) in a conventional manner, more specifically, the compound (e-2) is reacted with methyl chloride as a reagent in methylene chloride, while cooling with ice, in the presence of triethylamine as a base. (f) via compound (e) spontaneously under the same system at the same time Compounds (g) and (h) can be prepared as follows. (s-i) Cs-2) (g-3) (£ -4) (&-s) - UUO? C I H OH (g-6) (g-7) ßÉ ^ Mi ^ ^ ^^ MiiMI The compound (g-1) and the compound (g-2) which are known in the literature and commercially available, are subjected to a Diels-Alder reaction in a conventional manner to provide the compound (g-3). The compound (g-3) is converted to the compound (g-4) by reduction with lithium aluminum hydride and the removal of the silyl protecting group. The portion of allylic alcohol in the compound (g-4) is oxidized with manganese dioxide in a conventional manner. The hydroxy groups of the resulting compound (g-5) are acetylated in acetic anhydride-pyridine as reagent followed by reduction of double bond in the ring with palladium-carbon. In this way, the compound (g-6) can be prepared easily. The reaction of the compound (g-6) to provide the compound (g-7) can be carried out under conditions similar to those used to condense the compounds of formula [2D] and the compounds of formula [3D]. In this reaction, alpha-thioglycerin is used as the compound of formula [3D]. After, the 1,2-diol group of the compound (g-7) is protected with a protecting group such as an acetal, a ketal or an orthoester. Preferably, the compound (g-7) is reacted with acetone or its activated derivative in the presence of an acid catalyst to provide the compound (g-8) wherein the 1,2-diol is protected with isopropylidene. Subsequently, the acetyl is removed by alkaline hydrolysis in a conventional manner to provide the compound (g-9). The sulfur of the compound (g-9) is oxidized to the sulfone. Therefore, the compound (g-10) is prepared. The reaction is carried out under conditions such that they are similar to those used for oxidation, but the hydroxy is not oxidized. When the hydroxy is oxidized to COOH, the compound (g) can be prepared in one step. The compound (g) can be prepared by oxidizing the hydroxy with an oxidizing agent. The oxidizing agent that can be used includes an inorganic acid such as permanganate, chromic acid, etc., preferably chromic acid. The compound (h) can be prepared by keeping the compound (g) under basic conditions similar to those used to condense the compounds of formula [2D] and the compounds of formula [3D], without adding the compounds of formula [3D] to the reaction system. The reagents that can be used advantageously for the reaction are an inorganic base such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, etc., and an organic base such as triethylamine, 1,8-diazabicyclo [5.4.0] -undeca-7-ene, etc., preferably a organic base such as triethylamine. The compound (i) is known and can be prepared, by For example, by the process described in J. Chem. Soc. (C), 2308 (1967). The compound (j) can be prepared by reacting the corresponding aldehyde with an acrylic acid derivative in the presence of a catalyst such as sodium cyanide or 3-benzyl-5- (2-hydroxyethyl) -4-methylthiazolium chloride, etc. . (Chem. Ber., 109, 289, 541 (1976)) and then subjecting the reaction product to the Mannich reaction. The compound (p) can be prepared by subjecting the known 5-oxo-5-phenylpentanoic acid to the Mannich reaction. The compounds (q) and (s) are commercially available, for example from Tokyo Kasei K.K. the compound (r) can be prepared easily by heating the compound (q) in methanol in the presence of an acid catalyst. As the acid catalyst, there are the inorganic acids such as hydrochloric acid, sulfuric acid, etc., an organic acid such as p-toluenesulfonic acid or a Lewis acid such as boron fluoride etherate, etc., preferably an organic acid such as p-toluenesulfonic acid.

[E] Process for preparing the compound of formula [1E1 The compound of formula [ÍE] (hereinafter sometimes referred to as the physiologically active NA substance) can be prepared by culturing a strain that produces NA32176 belonging to the genus Streptomyces to produce and accumulate the physiologically active substance NA32176A and collect the substance NA32176A physiologically active of the culture solution. Representative examples of bacteria capable of producing the physiologically active substance NA32176A have the following microbiological and physiological properties. 1. Morphological properties When observed after incubation at 27 ° C for 2 weeks, the aerial mycelia simply branch out and form spirals or similar hooks on top. No sporangia, no whorled branches. Nor are zoospores observed. The surface of the spores is flat or rough. The spores are cylindrical and have a size of 0.7 to 0.9 x 1.3 μm. Spores are formed in more than 20 chains. 2. Growth in various media Table 1 below shows the growth conditions at 27 ° C for 2 weeks in various media.

Table 1 a = Sass-, Physiological properties 1) Optimal growth temperature interval: 24 ~ 37 ° C 2) Nitrate reduction: negative 3) Gelatin liquefaction (glucose-peptone-gelatin medium, 20 ° C): pseudo-positive 4) Starch hydrolysis (medium of starch-inorganic salt-agar): positive 5) Solidification of skimmed milk: negative 6) Peptonization of skimmed milk: positive 7) Melanoid pigment formation: negative 4. Assimilation of carbon sources (Pridham-Gottlieb agar medium) L-arabinose + D-xylose + D-glucose D-fructose + Sucrose + Inositol L-rhamnose Raffinose D-mannitol 5. Diaminopimelic acid in the cell wall LL-diaminopimelic acid From the above results, the cell wall of this strain is LL-diaminopimelic acid; According to the International Strptomyces Project (abbreviated as ISP), the morphology of the spore forming mycelia belongs to the spiral section. The surface of the spores is flat or rough. The mycelia are of a series of gray and hygroscopic. No pigment similar to melanin is produced. The substrate mycelia show a light yellow or light brown color. The strain assimilates as sources of carbon L-arabinose, D-glucose, D-fructose, sucrose, raffinose, D-mannose, D-mannitol and D-xylose. Based on the above properties, an analysis is performed according to R.E. Buchanan &; N.E. Gibbons, Bergey's Manual of Determinative Bacteriology, eighth edition, 1974; and it is found that strain NA32176 belongs to the genus Streptomyces. Therefore, the strain is named Streptomyces sp NA32176. The strain is deposited at the National Institute of Bioscience and Human-Technology Agency of Industrial Science and Technology (No. 1-3, Higashi 1-chome, Tsukubashi, Ibaraki, Japan) on August 8, 1997 and the access number is received. FERM P-16372. After the deposition is transferred to an international deposition under the Budapest treaty on July 7, 1998 and receives as access number FERM BP-6411. The strain is capable of producing the physiologically active substance NA32176A of the present invention which has the neuron differentiation promoting activity mentioned above and belongs to the genus Streptomyces. Streptomyces sp. NA32176 (accession number FERM P-16372 in the National Institute of Bioscience and Human-Technology Agency of Industrial Science and Technology, international access number FERM BP-6411), which is isolated by the present inventors, is an example of the strains used more effectively in this invention. The strain belongs to the genus Streptomvces used in the present invention and are susceptible to change in its properties, like other strains belonging to the genus Streptomvces and therefore easily mutated by artificial mutation using, for example, UV rays, X-rays or chemical substances . Any mutant can be used for the present invention to the extent that it is capable of producing the physiologically active substance NA32176A of the present invention. * To produce the substance NA32176A according to the present invention, the strain described above is incubated aerobically in a medium containing nutrients that can assimilate Streptomvces. As sources of nutrients, the known nutrients used so far for the incubation of > * m ** ~ * * Xá mm m.

Streptomyces can be used. As carbon sources, there are glucose, fructose, glycerin, sucrose, dextrin, galactose, organic acids, etc., which can be used alone or in combination thereof. As sources of inorganic and organic nitrogen there are ammonium chloride, ammonium sulfate, urea, ammonium nitrate, sodium nitrate, peptone, meat extract, yeast extract, dry yeast, corn infusion liquor, soy bean powder , infusions of cotton seeds, casaamino acids, bacto-soyton, soluble vegetable protein, oatmeal, etc., which can be used alone or in combination. If necessary and desired, inorganic salts such as sodium chloride, calcium carbonate, magnesium sulfate, copper sulfate, iron sulfate, zinc sulfate, manganese chloride, and phosphoric acid salts may also be added to the system. , etc. In addition, organic materials such as amino acids, vitamins, nucleic acids and inorganic substances can also be appropriately supplemented in the culture system. For incubation, a liquid culture is more suitable, especially a culture with deep agitators. It is desired to perform incubation at a temperature of 20 ° C to 40 ° C in a pH range of slightly acidic to slightly alkaline nature.

^^^^^^^^^^^^ In liquid culture, incubation generally for 3 to 5 days results in the production and accumulation of the substance NA32176A in the culture broth. The incubation ends when the quantity of substance produced reaches the maximum. The cells are then separated from the medium by filtration and the product is purified and isolated. The purification and isolation of the filtrate product can be carried out by methods conventionally applied to the separation and purification of a metabolite from a microorganism of the cultured cells. That is, the culture broth is separated into the filtrate and the cells by conventional filtration. The filtrate is passed through a DIAION HP-20 column (trademark, Mitsubishi Chemical Industries, Ltd.) under alkaline conditions to adsorb the target substance. After washing with water, the column is eluted in a linear gradient from water to 80% hydrated methanol. The eluted active fraction is concentrated and the methanol is distilled off. The resulting concentrate is extracted with n-butanol under acidic conditions of hydrochloric acid. The n-butanol phase is concentrated in vacuo.

The concentrate is then subjected to chromatography on a Shepadex LH-20 column (trademark, Pharmacia Biotech) (mobile phase: methanol). The active fractions collected are concentrated and dissolved in a mixture of ethyl acetate-water (1: 1).

The solution is subjected to liquid-liquid centrifugal division chromatography (manufactured by Sanki Engineering K.K., CPC-LLB-M) using as a fixed phase the lower layer of the above mixture of ethyl acetate-water. After washing with the upper layer of the mixture, the active fraction is eluted inversely with the lower layer. Additional column chromatography on Sephadex LH-20 (mobile phase: methanol) gives NA32176A. The physicochemical properties of the substance NA32176A physiologically active obtained in this way are shown below. 1) Appearance: white powder 2) Molecular weight: 418 15 3) Molecular formula: C18H30N2O7S (determined by high resolution mass spectrum) 4) Solubility: soluble in a lower alcohol, water or dimethyl sulfoxide; insoluble in hexane or petroleum ether 5) Rf value by thin layer chromatography ODS: 0.7 with a developing solvent of n-butane: acetic acid; water (4: 1.2) 25 6) UV absorption spectrum: shows terminal absorption in water 7) IR absorption spectrum: Figure 1 shows the spectrum measured with a potassium tablet 8) Nuclear magnetic resonance spectrum of hydrogen: Figure 2 shows the spectrum measured in heavy water. 9) Nuclear magnetic resonance spectrum of carbon: Figure 3 shows the spectrum measured in heavy water. The chemical shift data are shown below. d (ppm) 223.5 (s), 180.1 (s), 176.4 (s) 175.1 (s), 77.0 (d), 69.6 (s), 53.4 (s), 47.7 (s), 39.8 (s), 39.7 (s) t), 38.9 (t), 36.7 (t), 36.5 (t), 32.5 (t), 31.0 (t), 25.7 (t), 21.8 (c), 20.3 (c) ) Color forming reaction: positive with phosphorus molybdate and palladium chloride.

The physiologically active substance NA32176A represented by the formula [ÍE] can also be prepared in a manner similar to the process for producing the compounds of formula [IB] described above.

In more detail, the physiologically active substance NA32176A can be easily produced by using pantethein (a product of cysteamine and pantothenic acid linked together) as the compound of formula [3B] and condensing panthenol under conditions similar to those used with the compounds (a ) a (f). Pantethein is known as Helv. Chim. Acta, 35, 1903 (1952) and can be easily prepared by hydrolysis of the S-benzoyl panthelin ester under alkaline conditions in a conventional manner.

[F] Process for preparing the compounds of formula [1F1 The compounds of the general formula [1F] can be prepared by reacting compounds of the general formula [2F]: (where A'F, B'F and Z'F have the same meaning as those defined in AF, BF and ZF but where the group contains a functional group, the functional group can be adequately protected), with compounds of formula general [3F]: HNXF Y'F [3F] (where X'F and Y'F have the same meaning as defined for XF and YF, but where it contains a functional group, the functional group may be adequately protected), and when required, remove the protective group. Most of the compounds of formula [3F] are commercially available. Specific examples of the compounds [3F] are piperidine, pyrrolidine, morpholine, N-methylpiperazine, N-phenylpiperazine, diethylamine, di-n-propylamine, diisopropylamine, etc. To carry out the above reaction, any condensation process can be used insofar as the compounds of formula [2F] can be condensed with the compounds of the formula [3F]. The reaction is generally carried out in an organic solvent, water or a mixture thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc .; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc .; a halogenated hydrocarbon such as methylene chloride, chloroform, etc .; a ketone such as acetone, methyl ethyl ketone, etc .; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc.

Preferred examples of the solvent to be used are an ether such as tetrahydrofuran or diethyl ether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or vinyl ethyl ketone, a polar aprotic solvent such as dimethyl sulfoxide or dimethylformamide, an alcohol such as methanol or ethanol or a mixture of such solvent and water. The reaction generally proceeds in the presence of a base or in the absence of any catalyst. The reagents used to maintain the basic conditions are an inorganic base, such as potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, etc., or an organic base such as triethylamine, 1, 8-diazabicyclo [5.4.0] -undeca- 7- ene, etc. These reagents are used in an amount of about 0.1 to 20 times the moles, preferably of way approximately 0.5 to 5 times the moles. The reaction temperature is not particularly limited insofar as the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between -50 ° C and 150 ° C. The compounds of Formula [2F] can be reacted with the compounds of formula [3F] in an equimolar amount. Practically, the compounds of formula [3F] can be used in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 240 hours, preferably 0.1 to 96 hours. k = ieüS &riw - * '- Compounds of the general formula [1F] can be easily prepared by reacting compounds of the general formula [4F]: (where A'F, B'F and Z'p have the same meaning as those defined in AF, BF and ZF but where the group contains a functional group, the functional group can be adequately protected), with compounds of formula general [3F]: HNXP Y '[3F] (where X'F and Y'F have the same meaning as defined for XF and YF, but where it contains a functional group, the functional group may be adequately protected), in the presence of formaldehyde or an equivalent thereof, and when it is required, remove the protective group. With respect to the details of the compounds of the formula [3F] the foregoing description applies to them.

The condensation process of the compounds of formula [4F] and the compounds of formula [3F] in the presence of formaldehyde or an equivalent thereof is referred to as the reaction of Mannich, details of which have already been described in various reviews (eg Tetrahedron, 46, 1791 (1990), Synthesis, 1973, 703). The reaction is generally carried out in an organic solvent, water or a mixture thereof. As the organic solvent, an aromatic hydrocarbon such as benzene, toluene, etc .; an alcohol such as methanol, ethanol, etc .; an ether such as tetrahydrofuran, diethyl ether, etc .; a halogenated hydrocarbon such as methylene chloride, chloroform, etc .; a ketone such as acetone, methyl ethyl ketone, etc .; an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, etc. Preferred examples of the solvent are an ether such as tetrahydrofuran or diethylether, a halogenated hydrocarbon such as methylene chloride or chloroform, a ketone such as acetone or methyl ethyl ketone, an aprotic polar solvent such as dimethyl sulfoxide or dimethylformamide, an alcohol such as methanol or ethanol, or a mixture of such solvent and water. The reaction generally proceeds in the presence of any catalyst. If necessary and desired, an acid can be used as a catalyst. Examples of formaldehyde equivalents are 1, 3, 5-trioxane and bis (dimethylamino) methane. The formaldehyde and its equivalents can be used in an amount of about 0.9 to 100 times the moles, preferably from 1 to 20 times the moles. The reaction temperature is not particularly limited so that the reaction can be carried out under cooling, at room temperature or with heating. Preferably, the reaction is carried out at a temperature between 0 ° C and 200 ° C. The compounds of formula [4F] can be reacted with the compounds of formula [3F] in an equimolar amount. Practically, the compounds of formula [3F] can be used in an excess amount, for example 1 to 2 times the moles. The reaction is carried out in 0.1 to 360 hours, preferably 0.1 to 120 hours. The compounds of the general formula [1F] can be easily prepared by reacting compounds of the formula [5F]: (where A'F, B'F and Z'F have the same meaning as defined in AF, BF and ZF, but when the group contains a functional group, the functional group can be adequately protected, and U is an outgoing group and the carbonyl in position 1 may be suitably protected), with compounds of general formula [3F] •.

HNX '[3F] • (where X'F and Y'F have the same meaning as defined for 5 XF and YF, and where it contains a functional group, the functional group may be adequately protected), and when required, the protective group is removed . The compounds of formula [3F] are defined herein in the foregoing. The reaction conditions used for the reaction are similar to those for the reaction of the compounds of formula [2F] and [3F]. Preferred examples of the leaving group are chloride, bromine, iodine, methanesulfonyloxy, chloromethanesulfonyloxy, t-fluoro-methanesulfonyloxy, chloromethanesulfonyloxy and (2,3-0-15-isopropylidene) propylsulfonyl. Specific examples of the compounds of formula [5F] are included below. (a) 2- [(2,3-O-isopropylidene) propylsulfonyl] -methyl-3-oxo-1-cyclopentanecarboxylic acid (b) 2 - [(2,3-O-isopropylidene) propylsulfonyl] -methyl-3 - methoxycarbonylcyclopentanone.

As a representative process for preparing the compounds of formula [2F] is described below. That is, the compounds of formula [2F] can be easily prepared by reacting the compounds of formula [4F]: (where A'F, B'F and Z'F have the same meaning defined in AF, BF and ZF, but where the group contains a functional group, the functional group can be adequately protected) with formaldehyde or an equivalent of it in the presence of a secondary amine, if necessary, while heating. The reaction conditions are similar to those used to react the compounds of formula [4F] with the compounds of formula [3F] described above. When additional heating is required, it is preferred to heat from 30 ° C to 200 ° C. Alternatively, compounds of formula [2F] can be easily prepared by producing the compounds of formula [1F] through the Mannich reaction, by oxidizing the nitrogen of the compounds [1F] with an oxidizing agent or by alkylating the same with an alkylating agent to turn it into a quaternary salt and then heat, if necessary. 25 The oxidizing agent suitable for use in oxidation includes a % Í SfSa: A it-4 !, &? AiM ^ iiáá? M »ttßuß?« ^ ßáQto- * tb «k" -'S? I8 ^ - í? ^^ k? organic peracid such as m-chloroperbenzoic acid, etc., hydrogen peroxide, an organic peroxide, etc. The alkylating agent includes methyl iodide, dimethyl sulfate, ethyl iodide, etc. The heating conditions optionally carried out after oxidation or alkylation are similar to those described above. In compounds of formula [4F] wherein A'F is, for example, an aliphatic hydrocarbon group regioselectively in the Mannich reaction, it can sometimes cause a problem. In this case, the problem can be avoided as follows. For example, the known 3-acetyl-butyrolactone (Bull, Chem. Soc. Jpn., 32, 1282 (1959) is kept under acidic or basic conditions to prepare 3-methylidene-4-oxo-ln-pentaneoic acid. used for the reaction are in an inorganic base such as sodium hydroxide, etc., an organic base such as triethylamine 1,8-diazabicyclo [5.4.0] -undeca-7-ene, etc., an inorganic acid such as acid hydrochloric, sulfuric acid, etc., an organic acid such as p-toluenesulfonic acid, preferably an organic base such as triethylamine or 1,8-diazabicyclo [5.4.0] -undeca-7-ene and an inorganic acid such as sulfuric acid To solve the radioselectivity problem, other alternatives can be used such as the processes described in J. Chem. Soc. Chem. Commun., 1974, 253 in which the highly site-selective reagents for the Mannich reaction are those that are used, or the process that involves the conversion site-specific of a ketone to an enolate followed by introduction of an aminomethylene unit into the enolate described in Tetrahedron, 46, 987 (1990). Some of the compounds of formula [4F] are commercially available as reagents. They are, for example, 4-phenyl-4-oxobutanoic acid, 4- (4-methylphenyl) -4-oxobutanoic acid, 4- (4-methoxyphenyl) -4-oxobutanoic acid, 2-methyl-4-oxo- 4-phenylbutyric acid, 3-benzoylbutyric acid, etc. Compounds of formula [4F] wherein AF is, for example, a benzene ring or a benzene ring substituted with an electron donor group can also be synthesized by Friedel-Crafts acylation with maleic anhydride in the presence of a Lewis acid catalyst. such as aluminum chloride (Org Synthesis, Coil III, 109 (1955)). The compounds of formula [4F] wherein AF is different from the groups described above, or the reduction products thereof (alcohol products) can be prepared by a modification of the Reformatsky reaction, which involves reacting the halide of corresponding acid of AF or the aldehyde with ethyl? -iodopropionate in the presence of zinc (J. Am. Chem. Soc., 109, 8056 (1987)). The reaction product can be oxidized to the corresponding ketone in a conventional manner to provide the compounds of formula [4F]. Alternatively, the compounds of formula [4F] can be The preparation is made by reacting the corresponding aldehyde of AF with acrylic acid derivatives in the presence of a catalyst such as sodium cyanide or 3-benzyl chloride. -5- (2-hydroxyethyl) -4-methylthiazolium, as described in Chem. Ber., 109, Section 289, 541 (1976). In addition, compounds of formula [4F] can be prepared by subjecting the corresponding methyl ketone of AF to condensation of Aldol with glyoxylic acid accompanied by dehydration in vacuo with heating, and by reducing the resulting carbon-carbon double bond in a conventional manner using, for example, zinc-acetic acid powders, as described in J. Med. Chem., 15, 918 (1972) The compounds of formula [5F] can be prepared, for example, according to the following process. [5F] where A'F, B'F and Z'F have the same meaning as those defined in AF, BF and ZF, but where the group contains a functional group, the functional group may be adequately protected, and U is a leaving group and the carbonyl in position 1 may be suitably protected. The compounds of formula (5F-a) can be prepared from the compounds of formula [4F] by a modification of the known processes for preparing a β-hydroxyketone, for example, by reacting the compounds of the formula [4F] with formaldehyde under basic conditions, or by reacting silyl-enol derivatives of the compounds of formula [4F] with formaldehyde under acidic conditions. The compounds of the formula [5F] can be prepared easily by reacting the compounds obtained in this way of the formula (5F-a) with a Sulfonyl chloride such as p-toluenesulfonyl chloride, if necessary, in the presence of a base, or by reacting with a halogenating reagent for the hydroxy, such as thionyl chloride, a triphenylphosphine-halogenating agent, a tphenylphosphine agent Diethylazodicarboxylate-halogenating agent, etc., in a conventional manner. The compounds prepared in this way of the formula [5F] can be used without the same isolates for the next reaction. The compounds (a) and (b) described above are the same as the compounds (c) and (d) in the preparation of the compounds «¡ÍES *. - * i ** * i, ». of formula [IB] and can be prepared by the process described for these compounds. Next, the pharmaceutical properties of the compounds of the present invention will be described in greater detail. The compounds of the present invention and the pharmacologically acceptable salts thereof are found to have a potent neurons differentiating promoter activity. Therefore, the compositions comprising as the active ingredient the compounds of the present invention and the pharmacologically acceptable salts thereof are effective to promote or accelerate the differentiation of neurons and can therefore be used as medicaments for the treatment of disorders nervous central and peripheral. When the compounds of the present invention and the pharmacologically acceptable salts thereof are used as an accelerator of neuron differentiation, the composition can be used in the form of pharmaceutical preparations such as injection, drops, granules, tablets, granules, fine particles. , powders, capsules, liquids, inhalation material, suppositories, eye lotion, poultice, ointment, spray, etc., alone or in combination with pharmaceutically acceptable additives such as carriers, diluents, dissolving aids, etc. The route for administration can be chosen from oral and parenteral administration (systemic and local administration). The compound of the present invention or a pharmacologically acceptable salt thereof contained in the pharmaceutical composition varies based on the form of the preparation, but preferably in an amount of 0.1 to 100% by weight. A dose is determined depending on the age, sex, but body, conditions of the patient and purpose of treatment, etc., but is generally in the range of about 0.01 to 500 mg / kg / day. Then, the processes for preparing the compounds of the present invention or pharmacologically acceptable salts thereof and the acceleration activity of neuron differentiation will be described in more detail below with reference to the following examples.

Example 1 Preparation of the acid 4- [(2R) - (2-acetylamino-2-carboxy) ethylthio] methyl-3-oxo-l-cyclopentanecarboxylic acid (Compound IA) (1) P r epa on of 1, 1-d ime t ox i-2 4-bis (methoxycarbonyl) cyclopentane (Compound IA- -B) and 1, 1- dimethoxy-2, 3-bis (methoxycarbonyl) - Cyclopentane (Compound lA-b) • 2, 4-Bis (methoxycarbonyl) cyclopentanone is prepared (composed to 1A-A) as a me z c la with 2, 3-bis (methoxycarbonyl) cyclopentanone (compound 1-Aa), for example by the process described in J. Org. Chem., 47, 2379 (1982). By converting the mixture to 2, 4- b i s (h i drox ime t i l) c i c l opononane and 2, 3 - 10 bis (hydroxymethyl) cyclopentanone, the two compounds can be separated from each other by silica gel column chromatography. To a mixture (6970 mg, 34.85 mmol) of the compound (1A-A) and compound (lA-a) is added (35 ml) of absolute methanol, (4.74 ml) of methyl orthoformate and (165 mg) of acid p-Toluenesulfonic monohydrate. The mixture is stirred at room temperature for 18 hours. After (60 ml) of toluene are added to the reaction mixture, the washing is carried out twice with (25 ml) of saturated sodium hydrogen carbonate. The toluene layer is washed with (50 ml) of a saturated aqueous solution of Sodium and concentrated to provide a mixture (8334 mg, yield: 97.2%) of 1,1-dimethoxy-2,4-bis- (methoxycarbonyl) cyclopentane (compound 1A-B) and 1,1-dimethoxy-2, 3- bis (methoxycarbonyl) cyclopentane (compound lA-b). í '~ § 2) Preparation of 2,4-bis (hydroxymethyl) -cyclopentanone (compound 1A-C) A solution of a mixture (9676 mg, 39.32 mmol) of the compound (1A-B) and the compound (Ia-b) in 10 ml of absolute ether is added dropwise to a suspension of 3120 mg of lithium aluminum hydride. in 43 ml of absolute ether, for one hour under cooling with ice. After stirring for 30 minutes, 3.12 ml of water, 3.12 ml of 15% sodium hydroxide and 3.12 ml of water are further added to the mixture, followed by stirring for an additional 30 minutes. 10 g of anhydrous sodium sulfate, 55 ml of ether and 6 g of HAIFURO SUPER CEL are added to the mixture. After stirring for 30 minutes, the mixture is filtered. The residue is further extracted twice with 100 ml of ether. All the ethereal fractions are collected and concentrated. The resulting residue is dissolved in 37 ml of acetone. 1.85 ml of water and 1.85 ml of 1 N hydrochloric acid are added to the solution. Then 1.85 ml of 1 N sodium hydroxide is added to the reaction mixture, 18 g of silica gel are added thereto followed by concentration. The residue is purified by silica gel column chromatography (550 ml, dichloromethane: methanol = 30: 1) to provide the compound (1A-C, 1310 mg, yield: 23.1%) and the compound (lA-c, 1539 mg, yield: 27.0%).

CCD (silica gel: chloroform: methanol = 10: 1): Compound (1A-C, Rf = 0.42), compound (lA-c, Rf = 0.45) (3) Preparation of 2,4-bis (acetoxymethyl) cyclopentanone (Compound 1A-D) To the compound (1A-C) (1130 mg, 7.847 mmol) are added (4 ml) of anhydrous pyridine and 4 ml of absolute acetic acid. The mixture is stirred at room temperature for 1 hour. The reaction mixture is then concentrated, and the residue is purified by silica gel column chromatography (150 ml of hexane: ethyl acetate = 1: 1) to provide the compound (1A-D) (1598 mg, yield: 89.2%).

XH NMR (200 MHz, CDC13) d: 1.45-1.70 (1H, m), 1.85-2.12 (7H, m), 2.15-2.78 (4H, m), 4.00-4.39 (4H, m). MS (BAR, POS) m / z: 229 (M + H) + (4) Preparation of 4-acetoxymethyl-2-. { (2,3-dihydroxy] propylthiolmethylcyclopentanine (Compound 1A-E) ml of methanol, 30 ml of acetone and 6.1 ml of 1 N sodium hydroxide are added to the compound (1A-D) (1.4 g, 133 mmol) and alpha-thioglycerol (0.66 g, 133 mmol). The mixture is stirred for 45 minutes. After the pH is adjusted to 7.0 by adding 1N hydrochloric acid to the reaction solution, the mixture is concentrated. 30 ml of the solution is added to the residue ^ fc aqueous saturated sodium chloride. The mixture is extracted 5 times with 30 ml of dichloromethane. The dichloromethane layer dries over anhydrous sodium sulfate followed by concentration. The residue obtained in this way is purified by silica gel column chromatography (300 ml, chloroform: methanol = 40: 1 to 10: 1) to provide the compound (1A-E) (1.5 g, yield: 88.23%) . 10 XH NMR (200 MHz, CDC13) d: 1.50 (1H, m), 1.78-2.28 (5H, m), 2.35-2.80 (8H, m), 2.85-3.08 (1H, m), 3.50-3.33 (1H , m), 3.68 - 3.90 (2H, m), 3.98 - 4.20 (2H, m) MS (BAR, POS) m / z: 277 (M + H) +. 15 (5) Preparation of 4-acetoxymethyl-2-. { (2,3-0- isopropylidene) propylthio} methylcyclopentanone (Compound 1A-F) To the compound (1A-F) (1.6 g, 5.78 mmole) are added (15 ml) of acetone, dimethoxypropane (1.81 g, 17.34 mmol) and p-toluenesulfonic acid monohydrate (0.11 g, 0.578 mmol). The mixture is stirred at room temperature for 2 hours. Then 20 ml of water and 80 ml are added to the reaction mixture of ethyl acetate, the pH of the aqueous phase is adjusted to 7.0 with saturated sodium hydrogen carbonate. Sodium chloride is added to the aqueous phase for separation until it is saturated. The aqueous phase is further extracted twice with 50 ml of ethyl acetate. The ethyl acetate layers are collected and dried over anhydrous sodium sulfate. The residue which is obtained after concentration is purified by silica gel column chromatography (300 ml, hexane: ethyl acetate = 3: 1) to give the compound (1A-F) (1.6 g, yield: 87.4%) .

XH NMR (200 MHz, CDC13) d: 1-35 (1H, s), 1.42 (3H, s), 1.85-2.26 (5H, m), 2.30-2.85 (7H, m), 2.95-3.12 (1H, m), 3.70 (1H, dd, J = 6.27 Hz, 8.22 Hz), 3.98-4.32 (4H, m) MS (BAR, POS) m / z: 317 (M + H) +. (6) Preparation of 4-hydroxymethyl-2- [(2,3-0- isopropylidene) propylthio] methylcyclopentanone (Compound 1A-G) To the compound (1A-F) (1.6 g, 5.05 mmol) is added 20 ml of methanol and 5 ml of water. To the mixture is added, under ice-cooling, 1 N sodium hydroxide (3.2 ml, 320 mmol), followed by stirring for 1 hour. The pH is then adjusted to 7.0 with 1 N hydrochloric acid, the reaction solution is concentrated and 15 ml of a saturated aqueous solution of sodium chloride are added to the residue. After extracting , ... jji SS ft- * ** - - ^ - "* fatís &ifcjia, ~ v»? S 3 times with 30 ml of ethyl acetate, the ethyl acetate layer is dried over anhydrous sodium sulfate and then concentrated to dryness The residue is purified by silica gel column chromatography, 250 ml, ethyl acetate: hexane = 2: 1) to provide the compound (1A-G) (1.0 g, yield: 72.4 %).

XH NMR (200 MHz, CDC13) d: 1.35 (3H, s), 1.42 (31H, s), 1.61 - 1.73 (1H, m), 1.95 - 2.85 (9H, m), 3.00 (1H, m), 3.60 - 3.78 (3H, 10 m), 4.05 - 4.12 (1H, m), 4.18 - 4.33 (1, m). MS (BAR, POS) m / z: 275 (M + H) + (71 Preparation of 4-hydroxymethyl-2- [(2, 3-0- isopropylidene) propylsulfonyl] met ilcyclopentanone (compound 1A-H) The compound (1A-G) (1.0 g, 3.64 mmol) is dissolved in 25 ml of dichloromethane. To the solution is added in four portions, under cooling with ice, m-chloroperbenzoic acid (1.74 g, purity 80%, 8.04 mmol). After stirring for 1.5 hours and subsequently filtering, 10 ml of water, 1 ml of 20% sodium hydrogen sulphite and 2 ml of saturated sodium hydrogen carbonate are added to the filtrate. The mixture is stirred at room temperature for 15 minutes. Then it is added to the reaction solution 20 ml of a saturated aqueous solution of Sodium chloride, and the mixture separates. The aqueous phase is extracted twice additionally with 25 ml of dichloromethane. The dichloromethane layers are collected and dried over anhydrous sodium sulfate and then concentrated. The residue is purified by silica gel column chromatography (300 ml, ethyl acetate: hexane = 3: 1) to give the compound (1A-H) (1.0 g, yield: 89.2%). (8) Preparation of 4- [(2, 3-O-isopropylidene) -propylsulfoni-11-methyl-3-oxo-1-cyclopentanecarboxylic acid (compound a) The compound (1A-H) (1.0 g, 3.26 mmol) is dissolved in 55 ml of acetone. While stirring, 2.5 ml of Jones's reagent is added dropwise to the solution over 15 minutes while cooling. The reaction solution is stirred for 20 minutes, during which the reaction solution retains an orange color. 1 ml of 2-propanol is added to the reaction mixture. After stirring for 5 minutes, the mixture is concentrated. To the residue is added 20 ml of water and 30 ml of a saturated aqueous solution of sodium chloride. The resulting mixture is extracted eight times with 40 ml of dichloromethane. The dichloromethane layer is washed with 200 ml of a saturated aqueous solution of sodium chloride. Dry over anhydrous sodium sulfate and then concentrate. The residue is purified by silica gel column chromatography (100 ml of chloroform-methanol = 10: 1 to 4: 1) to give compound (a) (0.69 g, yield: 66.3%).

XH NMR (200 MHz, CDC13) d: 1.37 (3H, s), 1.44 (1.5H, s), 1.45 (1.5H, s), 1.78-2.31 (1H, m), 2.32 - 3.51 (8H, m) , 3.75 (2H, m), 4.20 (1H, dd, J = 8.67 Hz, 8.71 Hz), 4.60 (1H, m), 6.80 (1H, broad s) MS (BAR, POS) m / z: 321 (M + H) + (9) Preparation of 4- [(2R) - (2-acetylamino-2-carboxy) ethylthiol methyl-3-oxo-1-cyclopentanecarboxylic acid (compound IA) Compound (a) (170 mg, 0.53 mmol) is dissolved in 7 ml of acetone. N-acetyl-L-cysteine is added to the solution (87 mg, 0.53 mmol) and 1.5 ml 1 N sodium hydroxide. The mixture is stirred at room temperature for 2 hours. Subsequently the pH is adjusted to 6.8 by adding 1 N hydrochloric acid to the reaction mixture and the mixture is concentrated. The residue is purified on QAE-Sephadex (200 ml, Cl type, 0.05M-0.4M aqueous sodium chloride solution, 700 ml of each, elution gradient) to obtain the target fraction. After the fraction is concentrated, 3 ml of methanol are added to filter out the insoluble salts. The filtrate is purified by Sephadex LH-20 . ^ --- ^. ^? (100 ml, 80% hydrated methanol) to provide the sodium salt of the compound (IA) (85 mg, yield: 46.1%).

* H NMR (200 MHz, CDC13) d: 108 (1H, m), 2.06 (3H, s), 2.10 - 2.80 (5H, m), 2.81 - 3.16 (4H, m), 4.36 (1H, dd, J = 44.4 Hz, 8.1 Hz) MS (BAR, POS) m / z: 348 (M + H) + Example 2 Preparation of 4- [(2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthiol methyl-3-oxo-1-cyclopentanecarboxylic acid (Compound 2A) Add 6 ml of acetone, N-acetyl-L-cysteine methyl ester (110.6 mg, 0.624 mmol), 2 ml of water and 1.25 ml of 1 N sodium hydroxide to compound (a) (200 mg, 0.624 mmol) .

The mixture is stirred at room temperature for 2 hours.

After the pH is adjusted to 6.8 by adding hydrochloric acid 1 N to the reaction mixture, the mixture is concentrated. The residue is purified in QAE-Sephadex (200 ml, Cl type, 0.05 M-0.03 M of an aqueous sodium chloride solution, 700 ml of each, elution gradient) to obtain the target fraction. After the fraction is concentrated, 3 ml of methanol are added to filter out the insoluble salts. The filtrate is purified by Sephadex LH-20 (100 ml, 80% hydrous methanol) to provide the compound (2A) as the sodium salt (140 mg, yield: 66.6%).

U NMR (200 MHz, CDC13) d: 1.80 (1H, m), 2.06 (3H, s), 2.08 -2.80 (5H, m), 2.81 - 3.18 (4H, m), 3.79 (3H, s), 4.64 (1H, m). MS (BAR, POS) m / z: 340 (M + H) + Example 3 Preparation of (2RS.4S) -2- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] methyl-4-hydroxy-1-cyclopentanone (compound 3A) il) Preparation of (4R) -2- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylthio] methyl-4-tert-butyldimethylsiloxy-2-cyclopenten-1-one (compound 3A-b) (4R) -2- (N, N-diethylamino) methyl-4-tert-butyldimethylsiloxy-2-cyclopenten-1-one (compound 3A-a) (370 mg, 1.24 mmol) is dissolved in 4 ml of methanol. Iodomethane (0.16 ml) is added to the solution, 2.48 mmol) followed by stirring at room temperature for 2 hours. After the reaction solution is concentrated, 3 ml of methanol and N-acetyl-L-cysteine methyl ester (220 mg, 1.24 mmol) are added to the residue. The mixture is stirred at room temperature for 1.5 hours. After the reaction solution is concentrated, the residue is purified by silica gel column chromatography (60 ml, dichloromethane: methanol = 40: 1) to give the compound (3A-b) (378 mg, yield: 75.7 %).

XH NMR (200 MHz, CDC13) d: 0.12 (3H, s), 0.14 (3H, s), 0.92 (9H, s), 2.07 (3H, s), 2.31 (1H, dd, J = 2, 11Hz, 18.31Hz), 2.80 (1H, dd, J = 5.99Hz, 18.31Hz), 2.99 (2H, m), 3.30 (2H, m), 3.78 (3H, s), 4.86 (1H, m), 4.92 (1H , m), 6.56 (1H, d, J = 7.69Hz), 7.29 (1H, m) MS (BAR, POS) m / z: 402 (M + H) + (2) Preparation of (4R) -2- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylthio] methyl-4-hydroxy-2-cyclopenten-1-one (compound 3A-c) 4 ml of methanol, 0.2 ml of water and Dowex 50 (type H +, 300 mg) are added to the compound (3A-b) (64 mg, 0.16 mmol). The mixture is stirred at room temperature for 20 hours. The reaction mixture is concentrated and the residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 20: 1) to give the compound (3A-c) (33.6 mg, yield: 73.6%). MS (BAR, POS) m / z: 288 (M + H) + (3) Preparation of (4R) -2- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylsulfonyl methoxy-4-hydroxy-2 - cyclopenten-l-one (compound 3A-d) The compound (3A-c) (33.6 g, 0.117 mmol) is dissolved in 3 ml of dichloromethane. M-chloroperbenzoic acid (purity 80%, 50 mg, 0.23 mmol) is added to the solution under cooling with ice. After stirring at room temperature for 2 hours, 5 ml of water and 5 ml of dichloromethane are added to the reaction mixture. A saturated solution of sodium hydrogen carbonate is then added to the mixture until the aqueous layer becomes neutral. Sodium acid sulfite is added (20% aqueous solution, 5 drops) to the mixture for separation.

After the dichloromethane layer has been concentrated, the residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 10: 1) to provide the compound (3A-d) (36 mg, yield: 96.4%). MS (BAR, POS) m / z: 320 (M + H) + (4) Preparation of (4S) -2- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylsulfonyl] methyl-4-hydroxycyclopentan-1-one (compound c) To the compound (3A-d) (36 mg, 0.112 mmol) is added 3 ml of ethanol, 1.5 ml of methanol and 10% Pd-C (50% wet, 8.8 mg). The mixture is stirred at room temperature for hours in a hydrogen atmosphere. The reaction solution is filtered and the filtrate is concentrated to provide compound (c) (36 mg, yield: 100%). MS (BAR, POS) m / z: 322 (M + H) + (5) Preparation of (2RS, 4R) -2- [(2R) - (2-acetylamino-2-carboxy) ethylthio] methyl-4-hydroxy-1-cyclopentanone (compound 3A) 3 ml of acetone, N-acetyl-L-cysteine (24.3 mg, 0.149 mmol), 1.5 ml of methanol and 1 N sodium hydroxide (0.22 ml) are added to compound (c) (48 mg, 0.149 mmol). The mixture is stirred at room temperature for 1.5 hours. After 500 mg of silica gel has been added to the reaction solution, the mixture is concentrated to dryness. The residue is purified by silica gel column chromatography (80 ml, dichloromethane: methane: acetic acid = 5: 1: 0.1) and concentrated again. The residue is dissolved in 4 ml of water. After adjusting the pH to 6.8 with 1 N sodium hydroxide, the solution is concentrated to provide the sodium salt of the compound (3A) (26.6 mg, yield: 60%).

? E NMR (200 MHz, D20) d: 1.76 (1H, m), 2.00 (3H, s), 2.20 (1H, dd, J = 7.13Hz, 18.9Hz), 2.30 - 3.16 (8H, m), 4.40 - 4.62 (2H, m). MS (ESI, NEG) m / z: 274 (M-H) + 5 Example 4 (2RS.4S) -2 - [(2R) -3-acetylamino-3-T1-Y2S) -methoxycarbonyl} pyrrolidinyl] -3-oxopropylthio] methyl-4-hydroxy-1- cyclopentanone (compound 4A) The compound is dissolved in 3 ml of dimethylformamide (3) (28.2 mg, 0.1 mmol) and 16.95 mg of proline methyl ester hydrochloride. Under cooling with ice, they are added to the solution 14.1 μl of triethylamine, 1-hydroxy-benzotriazole (16.5 mg, 0.2 mmol) and 23.1 mg of dicyclohexylcarbodiimide. The mixture is stirred at room temperature for 2 hours. The reaction solution is concentrated and the residue is purified by silica gel column chromatography (30 ml,20 dichloromethane: methanol = 10: 1) to provide the compound (4A) (18.2 mg, yield: 47%).

XH NMR (200 MHz, CDC13) d: 1.85 - 2.10 (3H, m), 2.00 (3H, s), 2.10 - 3.13 (10H, m), 3.64 - 3.90 (5H, m), 4.42 - 4.70 (2H, m), 25 4.98 (1H, m), 6.68 (1H, m) MS (BAR, POS) m / z: 387 (M + H) + Example 5 2- ((2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthio) -methyl-3-oxo-1-indanecarboxylic acid (compound 6A) After 37% formalin (0.088 ml, 1.08 mmol) is added to a mixture of 3-oxo-1-indanecarboxylic acid (191 mg, 1.08 mmol) and piperidine (92.3 mg, 1.08 mmol), the mixture is stirred at room temperature. environment for 3 hours. The reaction solution is concentrated. 3 ml of ethanol and the N-acetyl-L-cysteine methyl ester (80 mg, 0.45 mmol) are added to the residue. The residue is refluxed for 10 minutes and then concentrated in vacuo. The residue is purified by silica gel column chromatography (100 ml, chloroform: methanol: acetic acid = 30: 1: 0.5) to give the compound (6A) (62 mg, yield: 15.7%).

* H NMR (200 MHz, CDC13) d: 2.05 - 2.12 (3H), 2.63 - 3.30 (4H, m), 3.42 (1H, m), 3.74 - 3.81 (3H), 4.21 (1H, d, J = 4.4 Hz), 4.89 (1H, m), 6.66-6.80 (1H, NH), 7.25 (1H, broad s), 7.41-7.86 (4H, m) MS (BAR, POS) m / z: 366 (M + H ) + Example Acid (IR, 2 S) -2- [(2R) -. { 2-Acetylamino-3-oxo-3- (1-pyrrolidinyl)} propylthio] methyl-3-oxo-1-cyclopentanecarboxylic (compound IB) (1) (2R, 3R) -3-acetoxymethyl -2- [(2RS) -2, 3-bis (hydroxypropylthiol methylcyclopentanone (compound A-2) Alpha-thioglycerin (9.558 g, 90.17 mmol) is added to a solution of (2R, 3R) -2, 3-bis (acetoxymethyl) -cyclopentanone (compound A) (20.56 g, 90.17 mmol) in 178 ml of acetone.

Then 20 ml of methanol and 90.17 ml of 1 N sodium hydroxide are added to the mixture, followed by stirring at room temperature for 40 minutes. After the pH is adjusted to 7.0 by adding 1N hydrochloric acid to the reaction solution, the mixture is concentrated. The residue obtained is dissolved in 200 ml of methanol and 120 g of silica gel are added to the solution. The mixture is concentrated to dryness, which is then purified by silica gel column chromatography (330 ml, dichloromethane: methanol = 25: 1 to 5: 1) to give the compound (A-2) (22.06 g, yield : 88.63%).

XH NMR (200 MHz, CD30D) d: 1.56 - 1.79 (1H, m), 2.07 (3H, s), 2.07 (3H, s), 2.10 - 2.16 (9H, m), 3.50 - 3.60 (2H, m) , 3.66 -3.78 (1H, m), 4.21 - 4.34 (2H, m) MS (BAR, POS) m / z: 277 (M + H) + (2) Preparation of (2S, 3R) -3-acetoxymethyl-2- [(2RS) - (2,3-isopropylidene) propylthio] methylcyclopentanone (compound A-3) The compound (A-2) (22.06 g, 79.92 mmol) is dissolved in 120 ml of anhydrous acetone. Under cooling with ice, 1.5 g of p-toluenesulfonic acid monohydrate, and dimethoxypropane (29.46 ml, 240 mmol) are added to the solution. The mixture is stirred at room temperature for 30 minutes. After 150 ml of water and 300 ml of ethyl acetate are added to the reaction mixture, the pH of the aqueous phase is adjusted to 7.0 with saturated sodium hydrogen carbonate. The aqueous phase is extracted twice with 300 ml of ethyl acetate. The ethyl acetate layer is washed with 160 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated in vacuo to give the compound (A-3) (24.00 g, yield: 95.0% ). lf liMilItt MilTf XH NMR (200 MHz, CDC13) d: 1.35 (3H, s), 1.42 (3H, s), 1.51 - 1.76 (1H, m), 2.08 (3H, s), 2.10 - 2.96 (9H, m ), 3.65 - 3.74 (1H, m), 4.05 - 4.18 (1H, m), 4.18 - 4.29 (2H, m). MS (BAR, POS) m / z: 317 (M + H) + 5 (3) Preparation of (2S, 3R) -3-hydroxymethyl-2- [(2RS) - (2,3-isopropylidene) - propylthiol methylcyclopentanone (compound A-4) The compound (A-3) (25.22 g, 79.81 mmol) is dissolved in 253 ml of methanol. Under ice cooling, 50 ml of IN sodium hydroxide are added to the solution. The mixture is stirred at room temperature for 18 minutes. After the pH of the mixture is adjusted to 5.8 with IN hydrochloric acid while After cooling with ice, the mixture is concentrated in vacuo to provide the residue. 50 ml of water are added to the residue and the mixture is extracted 3 times with 200 ml of ethyl acetate. The ethyl acetate layer is washed with 100 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate, Anhydrous sodium is added and concentrated in vacuo. The residue obtained in this way is purified by silica gel column chromatography (300 ml, dichloromethane: methanol = 30: 1) to give the compound (A-4) (18.67 g, yield: 85.3%).

XH NMR (200 MHz, CDC13) d: 1.36 (3H, s), 1.43 (3H, s), 1.58-1.81 (1H, m), 2.00-2.82 (9H, m), 3.02-3.11 (1H, dd, J = 3. 6Hz, 13.2Hz), 3.64 - 3.73 (1H, m), 3.76 - 3.91 (2H, m), 4.06 - 4.34 (2H, m). MS (BAR, POS) m / z: 275 (M + H) + (4) Preparation of (2S, 3R) -3-hydroxymethyl-2- [(2RS) - (2, 3-0- isopropylidene) propylsulfonyl] met ilcyclopentanone (compound A-5) The compound (A-4) (5,558 g, 20.28 mmol) is dissolved in 55 ml of dichloromethane. Under cooling with ice, a solution of m-chloroperbenzoic acid (80% pure, 8.74 g, 40.56 mmoles) in 85 ml of dichloromethane is added to the solution. The mixture is stirred at room temperature for one hour. The reaction solution is filtered and 6.48 ml of 20% sodium hydrogen sulphite, 16.2 ml of a saturated aqueous sodium carbonate solution and 50 ml of additional water are added to the filtrate, followed by stirring for 10 minutes. After liquid-liquid separation, the dichloromethane layer is washed with 100 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue obtained in this way is purified by silica gel column chromatography (150 ml, hexane: ethyl acetate = "^ S-" "_ - ií" i? 38íí S !? < S-1: 3) to provide the compound (A-5) (5,798 g, yield 93.4%).

XH NMR (200 MHz, CDC13) d: 1.38 (3H, s), 1.45 (3H, s), 1.68 -1.92 (1H, m), 1.99-2.76 (6H, m), 3.10 - 3.50 (3H, m) , 3.70 -4.08 (4H, m), 4.10-4.24 (1H, dd, J = 6.14 Hz, 7.42 Hz), 4.56 -4.68 (1H, m). MS (BAR, POS) m / z: 307 (M + H) + (5) Preparation of the acid (IR, 2S) -2- [(2RS) - (2.3-0- isopropylidene) propylsulfonyl methyl-3-oxo-1-cyclopentanecarboxylic acid (compound C) The compound (A-5) (5.80 g, 18.94 mmol) is dissolved in 320 ml of acetone. While stirring, Jones' reagent is added to the solution until the reaction solution maintains its orange color. Under cooling with ice, 2-propanol is added to the reaction mixture until the reaction solution becomes green. The mixture is concentrated m vacuo to remove acetone. To the residue, 120 ml of water are added. The mixture is extracted twice with 200 ml of dichloromethane. The dichloromethane layer is washed with 80 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated in vacuo to give compound (C) (4.59 g, yield: 75.7%).

XH NMR (200 MHz, CDC13) d: 1.37 (3H, s), 1.43 (1.5H, s), 1.47. (1.4H, s), 2.02 (1H, m), 2.22 - 2.65 (3H, m), 2.94 - 3.32 (3H, m), 3.32 - 3.84 (4H, m), 4.19 (1H, m), 4.40 ( 1H, m), 4.59 (1H, m). MS (ESI, NEG) m / z: 319 (M + H) - (6) Preparation of the acid (IR, 2S) -2- [(2R) -. { 2-Acetylamino-3-oxo-3- (1-pyrrolidinyl)} propyl t io] met il-3-oxo-1-cyclopentanecarboxylic acid (compound IB) The compound (C) (32 mg, 0.1 mmol) is dissolved in 2 ml of acetone and a solution of (2R) -2-acetylamino-3 -oxo-3- (1-pyrrolidinyl) propanethiol (21.6 mg) is added thereto. , 0.1 mmol) in 1 ml of acetone. The mixture is stirred at room temperature for 2 hours. After the INN hydrochloric acid is added to the reaction solution to adjust the pH to 6.8, the mixture is concentrated. The residue is purified on QAE-Sephadex (Cl type, 110 ml, 0.05M-0.5M NaCl, 300 ml of each, elution gradient). The target fractions are collected. After the pH is adjusted to 2.6, the product is adsorbed on DIAION-SP207 (10 ml, Nippon Rensui K.K.), and then washed with water and eluted with 80% hydrated ethanol. After the pH is adjusted to 6. With sodium hydroxide IN, the eluent is concentrated to dryness to provide the sodium salt of the compound (IB) (26 mg, yield: 68.7%).

XH NMR (200 MHz, D20) d: 1.75 - 2.05 (5H, m), 1.98 (3H, s), 2.06 - 2.61 (3H, m), 2.62 - 3.25 (6H, m), 3.28 - 3.49 (2H, m), 3.52 -3.75 (2H, m), 4.69 (1H, t, J = 6.88 Hz) EM (ESI, NEG) m / z: 355 (M + Na) - Example 7 Preparation of the acid (IR, 2S) -2- f (2R) -. { 2-Acetylamino-3- (4-morpholinyl) -3 -oxo} propylthiol methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 2B) Compound (C) (32 mg, 0.1 mmol) is dissolved in 2 ml of acetone, and a solution of (2R) -2-acetylammo-3- (4-morpholinyl) -3-oxopropanothiol (23.2) is added thereto. mg, 0.1 mmol) in 1 ml of acetone. The mixture is stirred at room temperature for 1.5 hours. The purification is carried out in a manner similar to that of example 1 to provide the sodium salt of compound (2B) (22.4 mg, yield: 56.8%).

XH NMR (200 MHz, D20) d: 1.78 - 1.98 (1H, m), 1.99 (1H, s), 2.05 - 2.60 (3H, m), 2.65 - 3.00 (6H, m), 3.45 - 3.89 (8H, m), 4.90 (1H, t, J = 6.96) MS (BAR, POS) m / z: 395 (M + Na '+ H) + Example 8 Preparation of the acid (IR, 2S) -2- [(2R) -. { 2-Acetylamino-3 -oxo-3- (1-piperidiml) propyl 10.}. 1-metho-3-oxo-1-cyclopentanecarboxylic acid (compound 3B) Compound (C) (32 mg, 0.1 mmol) is dissolved in 2 ml of acetone. A solution of (2R) -2-acetylamino-3 - (1-piper? Din? L) -3-oxopropanotol (23 mg, 0.1 mmol) in 1 ml of acetone and 0.2 ml of acetone is added to the solution. sodium hydroxide The mixture is stirred at room temperature for 1.5 hours. The purification is carried out in a manner similar to that of example 6 to provide the sodium salt (26.0 mg, yield: 66.3%) of the compound (3B).

H NMR (200 MHz, C20) d: 1.40-1.72 (6H, m), 1.82 (1H, m), 1.98 (3H, s), 2.04 - 2.60 (3H, m), 2.62 - 3.20 (4H, m) , 3.32 - 3.70 (4H, m), 4.98 (1H, t, J = 7.04 Hz) MS (ESI, NEG) m / z: 369 (M-Na) - Example 9 Preparation of the acid (1R.2S) -2- [(2R) - (. {2-carboxy-2-pentafluoropropionylamino) ethylthio] -methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 4B) Compound (C) is dissolved (32 mg, 0.1 mmol) in 2 ml of acetone. A solution of (2R) -2-carboxy-2-pentafluoropropionylaminoethanethiol (25.3 mg, 0.1 mmol) in 1 ml of acetone, 1 ml of methanol and 0.3 ml of IN sodium hydroxide is added to the solution. The mixture is stirred at room temperature for 1.5 hours. The purification is carried out in a manner similar to that of example 1 to provide the sodium salt (30.0 mg, yield: 66.5%) of the compound (4B).

XH NMR (200 MHz, C20) d: 1.71 - 1.98 (1H, m), 2.05 - 2.60 (3H, m), 2.62 - 3.25 (6H, m), 4.41 (1H, dd, J = 4.19 Hz, 9.24 Hz) MS (ESI, NEG) m / z: 428 (M-Na) - EXAMPLE 10 Preparation of trans-2- [(2R) - (2-acetylamino-3-oxo-3- (1- pyrrolidinyl).] Ro-thyl-methyl-3-methoxycarbonyl-1-cyclopentanone (compound 5B) (5) Preparation of trans-3-acetoxy-2- [2,3-bis (hydroxy) propylthiol methylcyclopentanone (compound a-2) U n a n c e n t o n s - 2, 3 - 25 bis (acetoxymethyl) cyclopentanone (compound (a), 18.72 g, Mg ^ A .-. ^: S¡¡Í = iijÁéte ^^, ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡^ ^ ^ ^ ^ ^ aifc,: - 81.8 mmoles) in 160 ml of acetone is added to 8.7 g of alpha-thioglycerin. The mixture is stirred at room temperature for 20 minutes. The reaction solution is concentrated. The resulting residue is dissolved in methanol and 100 g of silica gel are added thereto followed by concentration. The residue is purified by silica gel column chromatography (300 ml, dichloromethane: methanol = 20: 1 to 5: 1) to give the compound (a-2) (21.88 g, yield: 96.8%).

XH NMR (200 MHz, CD30D) d: 1.56-1.79 (1H, m), 2.07 (3H, s), 2.10-2.96 (9H,), 3.56-3.60 (2H, m), 3.66-3.78 (1H, m) ), 4.21 - 4.34 (2H, m) MS (BAR, POS) m / z: 277 (M + H) + (2) Preparation of trans-3-acetoxy-2- [2,3-0-isopropylidene) propylthio] methylcyclopentanone (compound a-3) The compound (a-2) (21.9 g, 79.27 mmol) is dissolved in 120 ml of anhydrous acetone. Under cooling with ice, 1.4 g of p-toluenesulfonic acid monohydrate and 29.4 ml of dimethoxypropane are added to the solution. The mixture is stirred at room temperature for 30 minutes. After adding 140 ml of water and 280 ml of ethyl acetate to the reaction mixture, the pH of the aqueous phase is adjusted to 7.0 with saturated sodium hydrogen carbonate. The aqueous phase is extracted twice with 280 ml of ethyl acetate. The ethyl acetate layer is washed with 150 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated to provide compound (a-3) (23.34 g, yield: 93.2%) * H NMR (200 MHz, CDC13) d: 1.35 (3H, 1.42 (3H, s), 1.50 - 1.76 (1H, m), 2.08 (3H, m), 2.10 - 2.96 (9H, m), 3.65 - 3.74 (1H, m), 4.05 - 4.18 - 4.29 (2H, m) MS (BAR, POS) m / z: 317 (M + H) + (3) Preparation of trans-3-hydroxymethyl-2 [2. 3 -0- i sopropi l iden) propi l t io] met i l c i c lopentanone (compound a-4) The compound (a-3) (1097 mg, 3.47 mmol) is dissolved in 200 ml of methanol under cooling with ice and 3.47 ml of IN sodium hydroxide is added to the solution. The mixture is stirred at room temperature for 15 minutes. After the pH is adjusted to 7.0 with IN hydrochloric acid while cooling with ice, the mixture is concentrated. 3 ml of water are added to the residue obtained after extracting three times with 15 ml of ethyl acetate. The ethyl acetate layer is washed with 10 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue obtained is purified by silica gel column chromatography (50 ml, chloroform: methanol = 30: 1) to give the compound (a-4) (739 mg, yield: 77.5%).

XH NMR (200 MHz, CDC13) d: 1.35 (3H, s), 1.43 (3H, s), 1.58-1.81 (1H, m), 2.00-2.81 (9H, m), 3.02-3.11 (1H, dd, J = 3.5 Hz, 13.2 Hz), 3.64 - 3.73 (1H, m), 3.76 - 3.91 (2H, m), 4.06 -4.34 (1H, m) MS (BAR, POS) m / z: 275 (M + H ) + (4) Preparation of trans-3-hydroxymethyl-2- [2, 3-0-isopropylidene) propylsulfonyl methylcyclopentanone (compound a-5) The compound (a-4) (5140 mg, 18.76 mmol) is dissolved in 50 ml of dichloromethane. Under cooling with ice, a solution of m-chloroperbenzoic acid (8093 mg, 80% purity, 37.32 mmol) in 80 ml of dichloromethane is added to the solution. The mixture is stirred at room temperature for 2 hours. The reaction solution is filtered and the filtrate is added with 6 ml of 20% sodium hydrogen sulphite, 6 ml of a saturated aqueous sodium carbonate solution and 50 ml of additional water which are added followed by stirring. After the liquid-liquid separation, the dichloromethane layer is washed with 30 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue obtained in this way is purified by silica gel column chromatography (160 ml, hexane: ethyl acetate = 1: 3) to give the compound (a-5) (4610 mg, yield: 80.3%) X H NMR (200 MHz, CDC13) d: 1.37 (3 H, s), 1.46 (3 H, s), 1.73 -1.92 (1 H, m), 1.98 - 2.73 (6 H, m), 3.10 - 3.49 (3 H, m) , 3.68 -4.08 (4H, m), 4.16 - 4.24 (1H, dd, J = 6.14 Hz, 7.42 Hz), 4.56 -4.68 (1H, m) MS (BAR, POS) m / z: 307 (M + H ) + (5) Preparation of trans-2 - [(2,3-0- isopropylidene) ropil sulphon-11-methyl-3-oxo-1-cyclopentanecarboxylic acid (compound c) The compound (a-5) (2630 mg, 8.59 mmol) is dissolved in 150 ml of acetone. While stirring, it is added to Jones' reaction solution until the reaction solution turns orange. Under cooling with ice, 2-propanol is added to the reaction mixture until the reaction solution becomes green. The mixture is concentrated and 60 ml of water are added to the residue. The mixture is extracted three times with 100 ml of dichloromethane. The dichloromethane layer is washed with 40 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated to provide compound (c) (1948 mg, yield: 70.8%).

"H NMR (200 MHz, CDC13) d: 1.37 (3H, s), 1.43 (1.5H, s), 1.47 (1.5H, s), 2.02 (1H, m), 2.22 - 2.65 (3H, m), 2.94 - 3.32 (3H, m), 3.32 - 3.84 (4H, m), 4.19 (1H, m), 4.40 (1H, m), 4.59 (1H, m) MS (ESI, NEG) m / z: 319 (MH) - (6) Preparation of trans-2- [) 2R) -. { 2-Acetylamino-3-oxo-3- (1-pyrrolidinyl) -propylthiol methyl-3-methoxycarbonyl-1-cyclopentanone (compound 5B) Compound (c) (32 mg, 0.1 mmol), (2R) -2-acetylamino-3-oxo-3- (1-pyrrolidinyl) -15-propanothiol (21.6 mg, 0.1 mmol) and 0.2 ml of hydroxide are reacted sodium, and purified in a manner similar to that of Example 1 to provide trans-2- [(2R) -. { 2-Acetylamino-3-oxo-3- (1-pyrrolidinyl)} ethylthio] methyl-3-oxo-l-cyclopentanecarboxylate sodium. The product is dissolved in 3 ml of DMF and added to the Same 20 μl of methyl iodide followed by stirring at room temperature for 35 minutes. The reaction solution is concentrated to dryness. The residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 25: 1) to give compound (5B) (18 mg, yield: 48.6%). 25 H NMR (200 MHz, CDC13) d: 1.80-2.10 (5H, m), 2.00 (3H, s), 2.10 - 2.60 (3H, m), 2.68 - 3.20 (6H, m), 3.38 - 3.70 (4H, m), 3.75 (3H, s), 4.90 (1H, m), 6.58 (1H, d, J = 8.34 Hz) MS (BAR, POS) m / z: 371 (M + H) + Example 11 Preparation of trans-2- [(2R) - [2-acetylamino-3 -. { 1- ((2S) -2-methoxycarbonylpyrrole idinyl)} -3 -oxo] propylthiol methyl-3 -oxo- 1- ^ B 10 cyclopentanecarboxylic (compound 6B) Compound (c) (53 mg, 0.165 mmol) and (2R) -2- acetylamino-3- [1 -. { (2S) -2-methoxycarbonyl] pyrrolidinyl} - 3 - 15 oxopropanothiol (43.5 mg, 0.165 mmol) are dissolved in 3 ml of acetone. 1 ml of methanol and 0.33 ml of sodium hydroxide IN are added to the solution. The mixture is stirred at room temperature for 1.5 hours. After IN hydrochloric acid is added to the reaction mixture to adjust the pH to 2.5, the mixture is concentrate to dryness. The residue is purified by silica gel column chromatography (25 ml, dichloromethane: methanol = 10: 1) to give compound (6B) (40.3 mg, yield: 58.9%). fifi ^^^ 7 &i ^ £ £ ssé ^ ^ ^ ^ Zi ^ ^ S ¿XH NMR (200 MHz, CDC13) d: 1.80 - 2.55 (8H, m), 2.01 - 2.02 (3H, sx2), 2.56 - 3.42 (6H, m), 3.62 - 4.00 (5H, m), 4.50 (1H, m), 4.75 - 5.19 (1H, m), 7.207.52 (1H, m), 7.80 (1H, broad s) EM (ESI, NEG) m / z: 414 (MH) - Example 12 Preparation of trans-2- {(2R) - [2-acetylamino-3-. { 1- ((2S) -2-methoxycarbonylazetidinyl)} 3-Oxol-propylthiol methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 7B) Compound (c) (92 mg, 0.288 mmol) and (2R) -2-acetylamino-3- [l-. { (2S) -2-methoxycarbonyl] azetidinyl} - 3-oxopropanothiol (75.0 mg, 0.288 mmol) is dissolved in 3 ml of acetone. 1 ml of methanol and 0.58 ml of sodium hydroxide IN are added to the solution. The mixture is stirred at room temperature for 1.5 hours. After 1N hydrochloric acid is added to the reaction mixture to adjust the pH to 2.5, the mixture is concentrated to dryness. The residue is purified by silica gel column chromatography (25 ml, dichloromethane: methanol = 10: 1) to give the compound (7B) (43.0 mg, yield: 373 mg).

XH NMR (200 MHz, CDC13) d: 2.00 (3H, sx2), 2.08 - 3.60 (12H, m), 3.76 - 3.84 (3H.sx2), 3.99 - 4.55 (2H, m), 4.60 - 5.35 (2H, m), 7.12 - 7.50 (1H, m), 7.90 - 8.60 (1H, broad s) MS (ESI, NEG) m / z: 399 (MH) - Example 13 Preparation of trans-2-T (2R) - (2-carboxy-2-pentaf luoropropionylamino) ethyl thiol methyl-3-hydroxymethyl-1-cyclopentanone (compound 8B) Compound (c) (45.6 mg, 0.2 mmol) is dissolved in 4 ml of acetone. To the solution (2R) -2-carboxy-2-pentafluoropropionylaminoethanethiol (50.6 mg, 0.2 mmol) in 1.5 ml of methanol and 0.8 ml of IN sodium hydroxide are added. The mixture is stirred at room temperature for 1 hour. After IN hydrochloric acid is added to the reaction mixture to adjust the pH to 2.5, the mixture is concentrated to dryness. The residue is purified in a manner similar to that of Example 1 to provide compound (8B) (71 mg, yield: 83.1%).

XH NMR (200 MHz, D20) d: 1.50 - 1.76 (1H, m), 2.20 - 2.65 (5H, m), 2.70 - 3.00 (3H, m), 3.50 - 3.90 (2H, m), 4.43 (1H, m) MS (BAR, POS) m / z: 416 (M + H) + 21 L \ Example 14 Preparation of trans-2- [(11-acetylamino-11-carboxy) undecylethiol methyl-3-oxo-l-cyclopentanecarboxylic acid (compound 9B) (1) Preparation of 1-acetylamino-11-benzyloxy-1, 1-diethoxycarbonylundecane (compound r-2) .5 ml of anhydrous ethanol and diethylacetamide malonate (2661 mg, 12.25 mmol) are added to sodium ethoxide (834 mg, 12.25 mmol). After stirring for 10 minutes, 1-benzyloxy-10-iododecane (Compound C-1) (2661 mg, 12.25 mmol) is added to the mixture. The mixture is refluxed for 4 hours and concentrated in vacuo. 200 ml of chloroform and 100 ml of water are added to the residue for separation. The organic layer is washed with 100 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue is purified by silica gel column chromatography (300 ml, hexane: ethyl acetate = 4: 1) to give the compound (r-2) (5080 mg, yield: 89.7%).

XT NMR (200 MHz, CDC13) d: 1.05 - 1.42 (18H, m), 1.60 (4H, m), 2. 02 (3H, s), 2.30 (2H, m), 3.48 (2H, t, J = 6.64 Hz), 4.26 (4H, c, J = 7.08 Hz), 4.50 (2H, s), 6.78 (1H, s broad), 7.30 (5H, m) (2) Preparation of 1-acetylamino-l, 1-diethoxycarbonyl-11-hydroxyundecane (compound r-3) The compound (r-2) (5090 mg, 10.99 mmol) is dissolved in 132 ml of ethanol and 10% Pd-C solution (50% wet, 1100 mg) is added to the solution. The mixture is stirred at room temperature for 3 hours in a hydrogen atmosphere. The reaction solution is filtered and the filtrate is concentrated to provide the compound (r-3) (3760 mg, yield: 91.7%).

MS (BAR, POS) m / z: 374 (M + H) + ?) Preparation of 1-acetylamino-1-carboxy-11-hydroxyundecane (compound r-4) The compound (r-3) (3760 mg, 10.08 mmol) is dissolved in 6 ml of ethanol. After the pH is adjusted to 2.0 with IN hydrochloric acid, the mixture is refluxed for 8 hours, during which pH is maintained at 2.0 by adding IN hydrochloric acid. The reaction solution is cooled to precipitate colorless crystals. The crystals are filtered to provide the compound (r-4) (1341 mg, yield: 48.7%).

MS (BAR, POS) m / z: 274 (M + H) + Preparation of 1-acetylamino-11-acetylthio-l-methoxycarbonylundecane (compound r-5) The compound (r-4) (176 mg, 0.64 mmol) is dissolved in 2 ml of methanol and TMS-diazomethane is added thereto. After reacting them for 15 minutes, the mixture is concentrated. The residue is added to a solution of 2-fluoro-1-methylpyridinium p-toluenesulfonate (190 mg, 0.637 mmol) in benzene: acetone (1: 3, 3 ml), and 88.6 μl of triethylamine is added thereto. The mixture is stirred at 30 ° C for 2 hours. 45.5 μl of thioacetic acid and 88.6 μl of triethylamine are added to the reaction solution. The mixture is refluxed for 2 hours. After the reaction solution is concentrated, 10 ml of dichloromethane and 5 ml of water are added to the residue for liquid separation. The aqueous layer is extracted twice with 10 ml of dichloromethane, the dichloromethane layers are collected, dried over anhydrous sodium sulfate and then concentrated. The residue obtained is purified by silica gel column chromatography (25 ml, dichloromethane) to give the compound (r-5) (222 mg, yield: 100%).

XH NMR (200 MHz, CDC13) d: 1.30 (15H, m), 1.47-1.96 (5H, m), 2.04 (3H, s), 2.33 (3H, s), 2.89 (2H, t, J = 7.04 Hz ), 3.76 (3H, s), 4.61 (1H, m), 6.02 (1H, d, J = 7.69 Hz). (5) Preparation of 1-acetylamino-1-carboxy-11-mercaptoundecane (compound r) The compound (r-5) (222 mg, 0.64 mmol) is dissolved in 3 ml of methanol and 1.3 ml of IN hydrochloric acid is added to the solution followed by stirring at room temperature for 2 hours. After the pH is adjusted to 3.0 with IN hydrochloric acid, the mixture is concentrated. The resulting residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 15: 1) to give the compound (r) (123 mg, yield: 66.9%). Example 15 Preparation of the acid (IR, 2S) -2- [(2R) -2-acetylamino-3-oxo-3-. { 1- (4-phenyl) piperazinyl-jpropylthio] methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 13B) -2-9-3 ml of methanolic solution of (2R) -2-acetylamino-3-oxo-3- [1 - (4-phenylpiperazinyl)] propanothiol (29.3 mg, 1 mmol), 1 ml of acetone and 0.2 ml of 1 N sodium hydroxide are added to compound (C) (32 mg, 1 mmol). The mixture is stirred at room temperature for 3 hours. After the pH is adjusted to 2.8 by adding 1 N hydrochloric acid to the reaction solution, 200 mg of silica gel is added thereto. The mixture is concentrated to dryness. The residue is purified by silica gel column chromatography (30 ml of chloroform: methanol = 10: 1) to give compound (13B) (28.5 mg, yield: 63.7%). 'H-NMR (200 MHZ, CDC13) d: 1.85, 2.13 (1H, m), 2.01 (3H, s), 2.06-2.60 (3H, m), 2.63-3.12 (6H, m), 3.68-3.92 ( 4H, m), 5.25 (1H, dd, J = 6.96 Hz, 15.02 Hz), 6.25 (1H, broad s), 6.93 (3H, m), 7.28 (2H, m), 7.48 (1H, d, J = 8.4 Hz). MS (BAR, POS) m / z: 448 (M + H) +.

Example 16 Preparation of the acid (1R, 2S) -2-. { 3- (3-pyridyl) propylthio} -methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 14B) Compound (C) (32 mg, 0.1 mmol) is dissolved in 1 ml of acetone and 1 ml of a methanolic solution of 3- (3-pyridyl) propanethiol (15.3 mg, 0.1 mmol) and 0.18 ml is added thereto. of sodium hydroxide 1 N. The mixture is stirred at room temperature for 3 hours. The mixture is concentrated and the residue is purified in QAE-Sephadex (Cl type, 110 ml, 0.05 M-0.5 M aqueous sodium chloride solution, 300 ml of each, 5 elution gradient). The target fractions are collected, after the pH is adjusted to 2.8, the product is absorbed in SEPABEADS SP207 (12 ml, Nippon Rensui K.K.), washed with water and eluted with 80% hydrated methanol. When collecting the target fractions, the compound (14B) is obtained (29.6 mg, yield: 10 89.8%). XH-NMR (200 MHZ, CD30D) d: 1.81-2.08 (3H, m), 2.10-2.60 (5H, m), 2.68-3.00 (5H, m), 3.08 (1H, m), 7.40 (1H, m ), 7.78 (1H, m), 8.40 (2H, m). MS (BAR, POS) m / z: 294 (M + H) +. 15 Example 17 Preparation of the acid (IR, 2S) -2- [3- (1-methylpyridinium iodide)} - propylthio] methyl-3-oxo-1-cyclopentanecarboxylic acid (compound 15B) Compound (C) (32 mg, 0.1 mmol) is dissolved in 1 ml of acetone. 1.5 ml of a methanolic solution of 3- is added to the solution. { 3- (1-methylpyridinium iodide)} propanothiol (30 mg, 0.1 mmol) and 1 N sodium hydroxide. The mixture is stirred at room temperature for 2 hours. After the reaction solution is concentrated, the residue is purified in a manner similar to that of Example 16 to provide the compound (15B) (17.8 mg, yield: 41%). XH-NMR (200 MHZ, CD30D) d: 1.85-2.10 (3H, m), 2.12-2.48 (3H, m), 2.48-2.86 (5H, m), 2.87-3.08 (3H, m), 4.42 (3H , m), 7.99 (1H, dd, J = 6.23 Hz, 7.69 Hz), 8.48 (1H, d, J = 7.69 Hz), 8.76 (1H, d, J = 6.23 Hz), 8.89 (2H, m). MS (BAR, POS) m / z: 308 (M + H) +.

Example 18 Preparation of 5- [(2R) - (2-Acetylamino-2-carboxy) ethylthio] -methyl-2-cyclopenten-1-one (compound IC) (i; Preparation of (4R) -2- i (2R) - (2-acetylamino-2-) -methoxycarbonyl) ethylthio] methyl-4-tert-butyldimethyl-siloxy-2-cyclopenten-1-one (compound a) Compound (c) (370 mg, 1.24 mmol) is dissolved in 4 ml of methanol and methyl iodide (0.16 ml, 2.48 mmol) is added to the solution. The mixture is stirred at room temperature for 2 hours. The reaction solution is then concentrated, and 3 ml of methanol and N-acetyl-L-cysteine methyl ester (220 mg, 1.24 mmol) are added to the residue. The mixture is stirred at room temperature for 1.5 h. The reaction solution is concentrated and the residue is purified by silica gel column chromatography (60 ml, dichloromethane: methanol = 40: 1) to give the compound (a-1) (378 mg, yield: 75.7%). XH-NMR (200 MHz, CDC13) d: 0.12 (3H, s), 0.14 (3H, s), 0.92 (9H, s), 2.07 (3H, s), 2.31 (1H, dd, J = 2.11 Hz, 18.31 Hz), 2. 80 (1H, dd, J = 5.99 Hz, 18.31 Hz), 2.99 (2H, m), 3.30 (2H, m), 3. 78 (3H, s), 4.86 (1H, m), 4.92 (1H, m), 6.56 (1H, d, J = 7.69 Hz), 7.29 (1H, m). MS (BAR, POS) m / z: 402 (M + H) +. (2) Preparation of (4R) -2 - [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylsulfonyl methyl-4-tert-butyldimethylsiloxy-2-cyclopenten-l-one (compound a-2) Compound (a-1) (378 mg, 0.94 mmol) is dissolved in ml of dichloromethane. Under cooling with ice, m-chloroperbenzoic acid (406 mg, 80% purity, 1.88 mmol) is added to the solution. After 15 ml of water and 3 ml of 20% sodium hydrogen sulphite are added to the reaction solution, saturated sodium hydrogen carbonate is added to the mixture until the pH of the aqueous layer becomes 7.0. The dichloromethane layer is washed with a saturated aqueous solution of sodium chloride and concentrated. The residue is purified by column chromatography on silica gel (50 ml of dichloromethane: methanol = 10: 1) to give (a-2) (355 mg, yield: 87.3%).

XH-NMR (200 MHz, CDC13) d: 0.13 (3H, s), 0.14 (3H, s), 0. 96 (9H, s), 2.08 (3H, s), 2.35 (1H, dd, J = 2.16 Hz, 18.52 Hz), 2. 86 (1H, dd, J = 5.94 Hz, 18.52 Hz), 3.65 (2H, d, J = 4.97 Hz), 3. 80 (3H, s), 3.81-4.16 (2H, m), 4.89-5.09 (2H, m), 6.70 (1H, broad d, J = 7.41 Hz), 7.66 (1H, m). MS (BAR, POS) m / z: 434 (M + H) +. (3) Preparation of (4R) -2 - [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylsulfonyl methyl-4-tert-butyldimethylsiloxy-2-cyclopentan-1-one (compound a) Compound (a-2) (355 mg, 0.82 mmol) is dissolved in 20 ml of ethanol and added to the 10% Pd-C solution (80 mg, 50% hydrated). The mixture is stirred at room temperature for 5 hours in a hydrogen atmosphere. The reaction solution is filtered and the filtrate is concentrated to provide compound (a) (330 mg, yield: 92.9%). MS (BAR, POS) m / z: 436 (M + H). (4) Preparation of (4R) -2- [(2R) - (2-acetylamino-2-carbonyl) ethylthiol methyl-4-tert-butyldimethylsilyloxy-2-cyclopentan-1-one (compound a-3) 2 ml of acetone, 8 ml of methanol, N-acetyl-L-cysteine (123.9 mg, 0.76 mmole) and 1.52 ml of 1 N sodium hydroxide are added to compound (a) (330 mg, 0.76 mmole). The mixture is stirred at room temperature for 2 hours. After the reaction solution is concentrated, purification is performed using Sephadex LH-20 (200 ml, 80% hydrated with methanol) to provide 299 mg of the compound (a-3). The compound is used for the subsequent reaction without further purification. (5) Preparation of 5- [(2R) - (2-acetylamino-2-carboxy) -ethylthio] methyl-2-cyclopenten-1-one (compound IC) ml of methanol, 1 ml of water and Dowex 50 (type H +, 300 mg) are added to the compound (a-3) (299 mg, 0.76 mmol). The mixture is stirred at room temperature for 20 hours. After filtration, 1 g of silica gel is added to the filtrate, followed by concentration. The resulting residue is purified by silica gel column chromatography (80 ml, dichloromethane: methanol: acetic acid = 5: 1: 0.1) to give the compound (C) (83 mg, yield: 39%). 'H-NMR (200 MHz, D20) d: 2.00 (3H, s), 2.45-3.16 (7H, m), 4.52 (1H, m), 6.20 (1H, m), 7.98 (1H, m). MS (BAR, POS) m / z: 258 (M + H) +.

Example 19 Preparation of (4R) -2- [(2R) - (2-acetylamino-2-carboxy) ethylthiol-methyl-4-hydroxy-2-cyclopenten-1-one (compound 2C) Add 2 ml of acetone, 4 ml of methanol, N-acetyl-L-cysteine (61.9 mg, 0.39 mmol) and (0.76 ml) 1 N sodium hydroxide to (4R) -2 - [(2R) - (2 Acetyl-lamino-2-methoxycarbonyl) ethylsulfonyl] methyl-4-tert-butyldimethylsiloxy-2-cyclopenten-1-one (165 mg, 0.38 mmol). The mixture is stirred at room temperature for 2 hours. After the reaction solution is concentrated, 5 ml of methanol, 1 ml of water and Dowex 50 (type H, 700 mg) are added to the residue followed by stirring at room temperature for 16 hours. After filtration, 500 mg of silica gel is added to the reaction mixture, which is then concentrated. The residue is purified by silica gel column chromatography (80 ml, dichloromethane: methanol: acetic acid = 5: 1: 0.1). After concentration, the residue is dissolved in 10 ml of water and 1 N sodium hydroxide is added thereto to adjust the pH to 6.9. Therefore, the sodium salt (61 mg, yield: 54.4%) of compound 2C is obtained. XH-NMR (200 MHz, D20) d: 2.00 (3H, s), 2.3 (1H, dd, J = 1.83 Hz, 18.83 Hz), 2.75-3.07 (3H, m), 3.32 (2H, s), 4.48 (1, dd, J = 4.76 Hz, 8.01 Hz), 4.98 (1H, m), 7.52 (1H, m). MS (ESI, NEG) m / z: 272 (M-Na) -.

Example 20 Preparation of 2- [(2R) - (2-acetylamino-2-carboxy) -ethylthiol-methyl-3-hydroxy-2-cyclopenten-1-one (compound 3C) N-Acetyl-L-cysteine (193 mg, 1.18 mmol), 2 ml of methanol, 4 ml of acetone and 2.36 ml of 1 N sodium hydroxide are added to compound (d) (347 mg, 1.18 mmol). The mixture is stirred at room temperature. 1 N sodium hydroxide is added to the mixture in portions until the reaction solution becomes neutral (4 hours). Then 1.2 g of silica gel are added to the reaction solution. The mixture is concentrated. The residue is purified by silica gel column chromatography (100 ml, dichloromethane: methanol: acetic acid = 5: 1: 0.1 to 2.5: 1: 0.1) to give the compound (3C) (308 mg, yield: 95.6% ). XH-NMR (200 MHz, D20) d: 2.00 (1H, s), 2.49 (4H, s), 2.72-2.99 (2H, s), 3.26 (2H, s), 4.38 (1H, dd, J = 4.68 Hz, 8.26 Hz). MS (BAR, NEG) m / z: 272 (M-H) - Example 21 Preparation of the acid 3-. { (2R) -2-acetylamino-2-carboxyethylthio} -4-oxo-1-n-pentanoic (compound ID) Compound (a) (256.3 mg, 2.00 mmol) is dissolved in 3 ml of tetrahydrofuran and added to the solution 1.8-- M &tii M? N diazabicyclo [5.4.0] -undeca-7-ene (609 mg, 4.00 mmol). The mixture is reacted overnight at room temperature. After 3 g of Amberlist-15 is added to the reaction mixture, the mixture is stirred for 5 minutes. Then the resin is separated by filtration. The filtrate is concentrated in vacuo. The residue is purified by silica gel column chromatography (40 ml, hexane: ethyl acetate = 3: 2 to 1: 1) to fractionate the fraction containing the compound. The fraction is concentrated in vacuo. The residue obtained is dissolved in 3 ml of tetrahydrofuran. N-acetyl-L-cysteine (107.7 mg, 0.66 mmol) and triethylamine (265.1 mg, 2.62 mmol) are added to the solution. After stirring at room temperature overnight, the reaction solution is concentrated in vacuo. The residue is purified by silica gel column chromatography (40 ml, methylene chloride: methanol = 10: 1 to 2: 1). The objective fraction is concentrated in vacuo and dissolved in tetrahydrofuran and 1 ml of methanol. 2 g of Amberlist-15 is added to the solution. After stirring the mixture for 3 minutes, the resin is filtered off and the filtrate is concentrated in vacuo. The residue is purified by silica gel column chromatography (40 ml, methylene chloride: methanol = 10: 1) to give the compound (ID) (40.9 mg, yield: 7%). 'H-NMR (200 MHz, DMS0-d6)) d: 1.86 (3H, s), 2.18 (3H, s), 2.4-2.6 (2H, m), 2.7-3.0 (4H, m), 3.05 (1H , m), 4.38 (1H, ddd, J = 8.1, 8.1, 5.1 Hz), 8.24 (1H, d, J = 8.1 Hz).

MS (BAR, POS) m / z: 292 (M + H) + In a similar manner to the above procedures, 3- acid can be prepared. { (2R) -2-acetylamino-2-methoxycarbonylethylthio} methyl-4-oxo-l-n-pentanoic (compound 2D). 'H-NMR (200 MHz, DMSO-d6) d: 1.86 (3H, s), 2.17 (3H, s), 2.4-2.7 (2H, m), 2.7-3.0 (4H, m), 3.04 (1H, m), 3.65 (3H, s), 4.46 (1H, ddd, J = 8.1, 8.1, 5.7 Hz), 8.39 (1H, d, J = 8.1 Hz). MS (BAR, POS) m / z 306 (M + H) + Example 22 Preparation of trans-2-. { (2R) -2-acetylamino-2-methoxycarbonylethylthio} methyl -3-ethoxycarbonyl-1-cyclobutanone (compound 3D) ?) Preparation of trans-2-hydroxymethyl-3-ethoxycarbonyl-1-cyclobutanone (compound e-2) Under cooling with ice, diisopropylamine (0.296 g, 2.92 mmol) is added to a solution of n-butyllithium (1.59 M hexane solution, 2.79 mmol) in 8 ml of tetrahydrofuran, and the mixture is stirred for 10 minutes. After cooling to -78 ° C, a solution of 3-ethoxycarbonyl-1-cyclobutanone (compound e-1) (355.4 mg, 2.50 mmol) in 3 ml of tetrahydrofuran is added dropwise to the mixture, which after stirring during 15 minutes. After the temperature is increased once at 0 ° CThe mixture is stirred for 15 minutes and cooled again to -78 ° C. Hexamethylphosphoramide is added to the system (535.8 mg, 2.99 mmol). After stirring for 5 minutes, a solution obtained by trapping formaldehyde subjected to cracking at 160 ° C and trapped in -78 ° C diethyl ether is poured into the system through a needle. The reaction ends with the addition of hydrochloric acid and the insoluble materials are filtered off. The filtrate is concentrated in vacuo. The residue is purified by silica gel column chromatography (50 ml, hexane: diethylether = 1: 1 to 1: 2) to give the compound (e-2) (50.7 mg, yield: 12%). 'H-NMR (60 MHz, CDC13) d: 1.30 (3H, t, J = 7 Hz), 2.17 (1H, broad), 3.23 (2H, m), 3.6-4.0 (4H, m), 4.20 (2H , c, J = 7 Hz). (2) Preparation of 2-methylidene-3-ethoxycarbonyl-1-cyclobutanone (compound f) The compound (e-2) is dissolved in 2 ml of methylene chloride. Under cooling with ice, triethylamine (60.1 mg, 0.59 mmol) and mesyl chloride are added to the solution. (36.7 mg, 0.32 mmol). The mixture is stirred for 30 minutes under the same conditions. Water and diethyl ether are added to the system for separation. The resulting organic layer is washed with water and then with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated in vacuo to provide compound (f) (40.3 mg, yield: 96%). 'H-NMR (60 MHz, CDC13) d: 1.33 (3H, t, J = 7 Hz), 3.30 (1H, dd, J = 15 Hz, 8 Hz), 3.40 (1H, dd, J = 15.6 Hz) , 4.00 (1H, m), 4.40 (2H, c, J = 7 Hz), 5.50 (1H, m), 6.03 (1H, m). (3) Preparation of trans-2-. { (2R) -2-acetylamino-2-methoxycarbonylethylthio} met il -3-ethoxycarbonyl-1-cyclobutanone (compound 3D) Compound (f) (40.3 mg, 0.26 mmol) 15 is dissolved in 2 ml of methylene chloride. Under cooling with ice, N-acetyl-L-cysteine (46.1 mg, 0.26 mmol) and triethylamine (10.9 mg, 0.11 mmol) are added to the solution. The mixture is stirred for one hour under the same conditions. The reaction solution is concentrated and the residue is purified by column chromatography on silica gel (20 ml, methylene chloride: methanol = 40: 1) and Sephadex LH-20 (10 ml, eluted with methanol) to provide the compound (3D) (27.4 mg, yield: 36.4%). 'H-NMR (200 MHz, CDC13) d: 1.31 (3H, t, J = 7.4 Hz), 2.07 (3H, s), 2.80 (2H, m), 3.0-3.5 (5H, m), 3.78 (3H , s), 3.84 (1H, m), 4.24 (2H, dd, J = 7.0, 1.7 Hz), 4.83 (1H, dt, J = 7.6, 4.9 Hz), 6.46 (1H, broad s, J = 6.3 Hz ). MS (BAR, POS) m / z: 332 (M + H) + Example 23 Preparation of trans-2- ((2R) -2-acetylamino-2-carboxyethylthio.} Methyl-3-oxo-1-cyclobutanecarboxylic acid (compound 4D) After 4 ml of an aqueous solution of 3 N hydrochloric acid are added to compound (3) (17.4 mg, 0.05 mmol), the mixture is stirred at room temperature overnight. The reaction solution is concentrated in vacuo. The residue obtained is purified twice by Sephadex LH-20 (100 ml and 200 mL, eluted with methanol) and twice by column chromatography on silica gel (2 mL, methylene chloride: methanol = 20: 1 to 2: 1) to provide the compound (4D) (6.0 mg, yield: 40 %). 'H-NMR (200 MHz, CD30D) d: 2.01 (3H, 2.80-4.0 (8H, m), 4.60 (1H, m). MS (BAR, POS) m / z: 290 (M + H) + Example 24 Preparation of trans-3-acetoxymethyl-2- (2,3-dihydroxypropylthio) methyl-1-cyclobutanone (compound 5D) (1) Preparation of 3 -acetoxymethyl-2-methylidene-1-cyclobutanone (compound d) After 3 ml of tetrahydrofuran and 1,8-diazabicyclo [5.4.01-undec-7-ene (25.5 mg, 0.168 mmol) are added to compound (c) (30 mg, 0.14 mmol), the mixture is stirred at room temperature for one hour. The reaction solution is purified by silica gel column chromatography (10 ml, hexane: ethyl acetate 2: 1) to give compound (d) (23 mg, yield: 95.5%). 'H-NMR (60 MHz, CDC13) d: 2.00 (3H, s), 2.65 3.30 (3H, m), 4.33 (2H, m), 5.30 (1H, d, J = 4.1 Hz), 5.80 (1H, d, J = 4.1 Hz). (2) Preparation of trans-3-acetoxymethyl-2- (2,3-dihydroxypropylthio) methyl-1-cyclobutanone (compound 5D) Compound (d) (23 mg, 0.133 mmoles) is dissolved in 1 ml of acetone and a solution of alpha-thioglycerin (11 μl, 0.133 mmole) in 1 ml of methanol is added to the solution. The mixture is stirred at room temperature for one hour. The reaction solution is concentrated. The obtained residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 20: 1) to give the compound (5D) (19 mg, yield: 51.3%). 5 'H-NMR (200 MHz, CDC13) 2.07, 2.10 (3H, sx2), 2.45- 3.45 (8H, m), 3.50-3.90 (3H, m), 4.33 (2H, m).

Example 24 Preparation of the acid 2-. { (2R) -2-acetylamino-2-carboxyethylthio} methyl-3-oxo-l-cyclohexanecarboxylic (compound 6D) (1) Preparation of 4,5-dimethoxycarbonyl 1 - 3 trimethylsiloxy-1-cyclohexane (compound g-3) The compound (g-1) (589 mg, 4.09 mmol) and the compound ( g-2) (588 mg, 4.09 mmol) is dissolved in benzene. The reaction is carried out at 150 ° C for 5 hours. After the reaction solution is concentrated, the residue is purified by column chromatography on silica gel (80 ml, hexane: ethyl acetate = 5: 1 to 3: 1) to give the compound (g-3) (875 mg, yield: 74.6%). 'H-NMR (200 MHz, CDC13) d: 0.05-0.12 (9H, m), 1.95-2.20 (1H, m), 2.70-2.94 (1H, m), 2.95-3.19 (1H, m), 3.68 ( 3H, m), 3.70 (3H, s), 4.50 (1H, m), 5.50-5.90 (2H, m). (2) Preparation of 4,5-bis (hydroxymethyl) -3-hydroxy-l-cyclohexane (compound g-4) Lithium borohydride is suspended in 25 ml of anhydrous tetrahydrofuran. Under cooling with ice, a solution of the compound (g-3) (875 mg, 3.05 mmol) in 4 ml of anhydrous tetrahydrofuran is added dropwise to the suspension. The reaction is carried out for 2 hours and then 0.196 ml of water, 0.196 ml of a 15% aqueous solution of sodium hydroxide and 0.59 ml of water are added to the mixture. Agitation is further continued. After the suspension is filtered, the filtrate is concentrated. The residue is purified by silica gel column chromatography (20 ml, methylene chloride: methanol 20: 1) to give the compound (g-4) (340 mg, 70.5%). (3) Preparation of 5,6-bis (hydroxymethyl) -2-cyclohexan-1-one (compound g-5) The compound (g-4) (320 mg, 2.02 mmol) is suspended in 20 ml of acetone. 1400 mg of manganese dioxide is gradually added to the solution. After the reaction, the precipitates are separated by filtration. The filtrate is concentrated and the residue is purified by silica gel column chromatography (40 ml, methylene chloride: methanol = 10: 1) to give the compound (g-5) (205 mg, 61.1%). 'H-NMR (200 MHz, CDC13) d: 2.30-2.60 (4H, m), 3.65 (2H, m), 3.76 (1H, dd, J = 3.67 Hz, 11.08 Hz), 4.10 (1H, dd, J = 3.67 Hz, 11.08 Hz), 5.98 (1H, dt, J = 2.12 Hz, 12.13 Hz), 7.08 (1H, m). (4) Preparation of 2,3-bis (acetoxymethyl) -cyclohexanone (compound g-6) ml of pyridine and 3 ml of acetic anhydride are added to the compound (g-5) (205 mg, 1.31 mmol). The mixture is reacted at room temperature for 2 hours. After the reaction solution is concentrated, the residue is subjected to silica gel column chromatography (20 ml, hexane: ethyl acetate = 1: 1). The fraction is concentrated and the concentrate is dissolved in 20 ml of ethanol. 50 mg of palladium-carbon (hydrated 50%) are added to the solution. The reaction is carried out at room temperature overnight under a hydrogen atmosphere. The catalyst is filtered off and the filtrate is concentrated. The residue is purified by silica gel column chromatography (30 ml, methylene chloride: methanol = 20: 1) to give the compound (g-6) (175 mg, 73.0%).

'H-NMR (200 MHz, CDC13) d: 1.70 (2H, m), 1.89-2.20 (3H, m), 2.02 (3H, s), 2.08 (3H, s), 4.13 (2H, m), 4.38 (2H, m) (5) Pr opar 3-acetoxymethyl-2- [2, 3- (dihydroxy) propylthio] methyl-1-cyclohexanone (compound g-7) Dissolve 2, 3-bis (acetoxymethyl) -1-cyclohexanone (compound g-6) (200 mg, 0.826 mmol) in 3 ml of acetone. A solution of alpha-thioglycerin (89.2 mg, 0.826 mmol) in 1 ml of methanol and 0.826 ml of IN sodium hydroxide are added to the solution. The mixture is stirred at room temperature for one hour. 1 g of silica gel is added to the reaction mixture.

After concentration, the residue is purified by silica gel column chromatography (30 ml, dichloromethane: methanol = 20: 1) to give the compound (g- 7) (175 mg, yield: 73.0%). MS (BAR, POS) m / z: 291 (M + H) + (6) Preparation of 3-acetoxymethyl-2- [(2.3-0- isopropylidene) propylthio] ethyl-1-cydohexanone (compound g-8) The compound (9-7) (170 mg, 0.586 mmoles) is dissolved in 1.5 ml of anhydrous acetone. P-Toluenesulfonic acid monohydrate (11 mg, 0.06 mmol), and dimethoxypropane (0.34 ml, 1.76 mmol) are added to the solution. The mixture is stirred at room temperature for 30 minutes. After adding 2 ml of water to the reaction mixture and adjusting the pH to 7.0 with saturated sodium hydrogen carbonate, the mixture is extracted three times with 5 ml of ethyl acetate. The organic layer is washed with 5 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated to provide the compound (g-8) (191 mg, yield: 98.7%). 'H-NMR (200 MHz, CDC13) d: 1.30 (3H, s), 1.39 (3H, s), 1.52- 2.15 (5H, m), 2.03 (3H, s), 2.20-3.05 (7H, m) , 3.67 (1H, m), 3.82-4.29 (4H, m). (7) Preparation of 3-hydroxymethyl-2- [(2,3-0- isopropylidene) propylthio] methyl-1-cydohexanone (compound g-9) The compound (g-8) (191 mg, 0.578 mmol) is dissolved in 2 ml of methanol. Under cooling with ice, 0.2 ml of water and 0.57 ml of sodium hydroxide IN are added to the solution. The mixture is stirred for 15 minutes while cooling with ice. When adding IN hydrochloric acid to the reaction mixture, the pH is adjusted to 6.8. 500 mg of silica gel are added to the system. The mixture is then concentrated and the residue is purified by silica gel column chromatography (20 ml, dichloromethane: methanol = 30: 1) to give the compound (g-9) (155 mg, yield: 93.1%). MS (BAR, POS) m / z: 289 (M + H) + (8) Preparation of 3-hydroxymethyl -2- [(2RS) - (2,3-isopropylidene) propylsulfonyl methyl-1-cyclohexanone (compound g-10) The compound (g-9) (155 mg, 0.538 mmol) was dissolved in 2 ml of dichloromethane. Under cooling with ice, ml of a dichloromethane solution of m-chloroperbenzoic acid (232 mg, purity 80%, 1.07 mmol) is added to the solution.

After the reaction mixture is filtered, 4 ml of water and 0.17 ml of 20% sodium hydrogen sulphite are added to the filtrate. HE add saturated sodium hydrogen carbonate to the mixture until the pH of the aqueous layer becomes 7.0. After the aqueous layer is extracted twice with 10 ml of dichloromethane, the dichloromethane layer is washed with 15 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrate. The residue is purified by silica gel column chromatography (18 ml, hexane: ethyl acetate = 1: 3) to give the compound (g-10) (151 mg, yield: 87.7%). MS (BAR, POS) m / z: 321 (M + H) + J¡L i At Ji * lS & M ^ (9) Preparation of 2- [(2,3-O-isopropylidene) -propylsulfoni-11-methyl-3-oxo-1-cyclohexanecarboxylic acid (compound g) The compound (g-10) (151 mg, 0.47 mmol) is dissolved in 9 ml of acetone. The Jones reagent is added to the solution until the solution turns orange. The mixture is stirred at room temperature for 10 minutes. Subsequently 2-propanol is added to the reaction mixture until it becomes green. The mixture is concentrated and 5 ml of water are added to the concentrate. The resulting solution is extracted 3 times with 5 ml of dichloromethane. The dichloromethane layer is washed with 10 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated to provide compound (g) (88.6 mg, yield: 56.4%). MS (ESI, NEG) m / z: 333 (M-H) - ? 0) Preparation of the acid 2-. { (2R) -2-Acetylamino-2-carboxyethylthiol methyl-3-oxo-1-cyclohexanecarboxylic acid (compound 6D) The compound (g) (88.6 mg, 0.265 mmole) is dissolved in 3 ml of acetone. N-acetyl-L-cysteine is added to the solution (43.2 mg, 0.265 mmol), IN sodium hydroxide (0.78 ml, 0.795 mmol) and 1 ml of methanol. The mixture is stirred for 2 hours at room temperature. After adjusting in pH of the mixture to 6.8 with IN hydrochloric acid, the residue is purified by Sephadex LH-20 (200 ml, 80% hydrated methanol) to provide the sodium salt (57.7 mg, yield: 60.3%) of the compound (6D). 'H-NMR (200 MHz, D20) d: 1.52-2.18 (4H, m), 2.00 (3H, s), 2.27-3.22 (8H, m), 4.28 (1H, dd, J = 4.03 Hz, 8.34 Hz) MS (ESI, NEG) m / z: 361 (M-Na) - Example 25 Preparation of 1 acid 3- [(2R) - (2-acetylamino-2-carboxy) ethylthiol methyl-4-oxo-4-phenylbutyric (compound 7D) N-acetyl-L-cysteine (39 mg, 0.24 mmol) and 4 ml of ethanol are added to 4-oxo-3- (1-piperidinyl) methyl-4-phenylbutyric acid (66 mg, 0.24 mmol). The mixture is refluxed for 2 hours. After the reaction mixture is concentrated in vacuo, water (5 ml) and ethyl acetate (8 ml) are added to the residue. The pH of the aqueous layer is adjusted to 2.0 with 1N hydrochloric acid followed by liquid-liquid separation. The mixture is extracted twice with 8 ml of ethyl acetate. The collected layers of ethyl acetate are washed with 5 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated in vacuo. The residue is purified by silica gel column chromatography (20 ml, chloroform: methanol = 20: 1) to give the compound (7D) (45 mg, yield: 53.1%). 'H-NMR (60 MHz, CD30D) d: 2.19 (1.5H, s), 2.20 (1.5H, s), 2.50-3.30 (6H, m), 4.16 (1H, m), 4.58 (1H, m) , 7.55 (3H, m), 8.00 (2H, m). MS (BAR, POS) m / z: 354 (M + H) + Example 26 Preparation g_e 3 - [(2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthio] methyl-4-oxo-4-phenylbutyric (compound 8D) N-acetyl-L-cysteine methyl ester (66.3 mg, 0.37 mmol) and 4 ml of 4-oxo-3- (1-piperidyl) methyl-4-phenylbutyric acid (103 mg, 0.37 mmol) are added successively. .

The mixture is heated to reflux for one hour. The reaction mixture is purified in a manner similar to that of Example 25 to provide the compound (8D) (116 mg, yield: 84.5%). 'H-NMR (60 MHz, CDC13) d: 2.01 (1.5 Hz, s), 2.03 (1.5H, s), 2.48-3.16 (6H, m), 3.70 (1.5H, s), 3.73 (1H, s), 4. 17 (1H, m), 4.85 (1H, m), 6.70 (1H, m), 7.52 (3H, m), 7.90 (2H, m). MS (BAR, POS) m / z = 368 (M + H) + Example 27 Preparation of the acid 3- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylthiol methyl-4- (4-methoxyphenyl) -4-oxobutyric (compound 9D) N-acetyl-L-cysteine methyl ester is added (66.3 mg, 0.37 mmol) and ethanol (3 ml) were added to 4- (4-methoxyphenyl) -4-OXO-3- (1-piperidyl) methyl-butyric acid (109 mg, 0.37 mmol). The mixture is refluxed for 2 hours. The purification is carried out in a manner similar to that of Example 25 to provide the compound (9D) (110 mg, yield: 73.4%). 'H-NMR (200 MHz, CDC13) d: 1.98 (1.5H, s), 2.05 (1.5H, s), 2.68 (2H, m), 2.90 (4H, m), 3.69 (1.5H, s), 3.72 (1.5H, s), 3.89 (3H, s), 4.02 (1H, m) , 4.80 (1H, m), 6.48-6.72 (1H, m), 6.98 (2H, d, J = 8.92 Hz), 7.40 (1H, broad s), 7.98 (2H, dd, J = 3.3 Hz, 8.92 Hz). MS (BAR, POS) m / z: 398 (M + H) + Example 28 Preparation of the acid 3-. { 2- (acetylamino) ethylthio} methyl-4- (4-methoxyphenyl) -4-oxobutyric (compound 10D) N-acetyl-L-cysteamine (45 mg, 0.37 mmol) and ethanol (3 ml) are added to the acid 4- (4-methoxyphenyl) -4 -oxo-3 - (1-piperidyl) methyl-4-phenylbutyric acid (109 mg, 0.37 mmol). The mixture is refluxed for 2 hours. The purification is carried out in a manner similar to that of Example 25 to provide the compound (10D) (93 mg, yield: 72%). 'H-NMR (200 MHz, CDC13) d: 1.98 (1.5H, s), 2.58-2.76 (4H, m), 2.90 (2H, m), 3.39 (2H, m), 3.89 (3H, m), 4.07 (1H, m), 6.12 (1H, t, J = 4.68 Hz), 6.60 (1H, broad s), 6.95 (2H, d, J = 8.9 Hz), 7.98 (2H, d, J = 8.9 Hz) . MS (BAR, POS) m / z: 340 (M + H) + Example 29 Preparation of the acid 3 -. { 2- (acetylamino) ethylthio} methyl-4-oxo-4-phenylbutyric (compound 11D) N-acetyl-L-cysteamine (45 mg, 0.37 mmol) and ethanol (3 ml) are added to 4-oxo-4-phenyl-3- (1-piperidyl) methylbutyric acid (103 mg, 0.37 mmol). The mixture is refluxed for 2 hours. The purification is carried out in a manner similar to that of Example 25 to provide the compound (11D) (83 mg, yield: 71.7%).

'H-NMR (200 MHz, CDC13) d: 1.97 (3H, s), 2.58-2.78 (4H, m), 2.90 (2H, m), 3.48 (2H, m), 4.11 (1H, m), 6.25 (1H, t, J = 5.21 Hz), 7.50 (3H, m), 7.98 (2H, m), 8.05 (1H, broad s). MS (BAR, POS) m / z: 310 (M + H) + Example 30 Preparation of 3- (2- (acetylamino) ethylthio.} Methyl-4- (4-methylphenyl) -4-oxobutyric (compound 12D) N-acetyl-L-cysteamine (57 mg, 0.47 mmol) and ethanol (3 ml) are added to the acid 4- (4-methylphenyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (131 mg, 0.47 mmol) . The mixture is heated to reflux. The purification is carried out in a manner similar to that of Example 25 to provide the compound (12D) (114 mg, yield: 73.6%). 'H-NMR (60 MHz, CDC13) d: 2.30 (3H, s), 2.70 (3H, s), 2.76-3.30 (4H, m), 3.30 4.15 (4H, m), 4.33 (1H, m), 6.70 (1H, t, J = 6.0 Hz), 7.50 (2H, d, J = 9.2 Hz), 7.80 (1H, broad s), 8.16 (2H, d, J = 9.2 Hz). MS (BAR, POS) m / z: 382 (M + H) + Example 31 Preparation of Acid 3 -. { (2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthiol methyl -4- (4-methylfinyl) -4 -oxobutyric (compound 13D) N-acetyl-L-cysteine methyl ester is added (92 mg, 0.52 mmol) and ethanol (3 mL) were added to 4- (4-methyl-fyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (142 mg, 0.52 mmol). The mixture is refluxed for 2 hours. The purification is carried out in a manner similar to that of Example 25 to provide the compound (13D) (126 mg, yield: 63.5%). 'H-NMR (60 MHz, CDC13) d: 2.30 (3H, s), 2.38 (1.5H, s), 2.80 (3H, s), 2.98-3.60 (6H, m), 4.01 (1.5H, s) , 4.10 (1.5H, s), 4.40 (1H, m), 5.14 (1H, m), 7.02 (1H, m), 7.41 (1H, broad s), 7.52 (2H, d, J = 8.5 Hz), 8.17 (2H, d, J = 8.5 Hz). MS (BAR, POS) m / z: 324 (M + H) + Example 32 Preparation of 3- [(2R) - (2-Acetylamino-2-methoxycarbonyl) ethylthiol methyl-4 -oxo-4- (3-pyridyl) butyric acid (Compound 32D) (1) Preparation of methyl 4-oxo-4- (3-pyridyl) butyrate (compound 32D-A) In a nitrogen atmosphere, a solution of 3-pyridinecarboxyaldehyde (10.7 g, 100 mmol) in anhydrous dimethylformamide (20 ml) was added. add drops to a solution of sodium cyanide (2.44 g, 50 mmol) at 30 ° C in anhydrous dimethylformamide (80 ml), for 30 minutes. After stirring for 30 minutes, a solution of methyl acrylate (8.6 g, 100 mmol) in anhydrous dimethylformamide (80 ml) is added dropwise to the reaction mixture for one hour, followed by stirring for 3 hours at 30 °. C. Acetic acid (0.66 ml) and water (30 ml) are added to the reaction solution. After stirring for 10 minutes, the mixture is concentrated in vacuo. Water (360 ml) and chloroform (300 ml x 3) are added to the residue for separation. The resulting organic phase is washed with a saturated aqueous solution of sodium chloride (300 ml), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is purified by silica gel column chromatography (650 ml, hexane: ethyl acetate = 1: 1 to 1: 2) to give the compound (32D-A) (7.87 g, yield: 40.7%). (2) Preparation of 4-oxo-4- (3-pyridyl) butyric acid (compound 32D-B) The compound (32D-A) (5.04 g, 26.11 mmol) is dissolved in methanol (60 ml). After adding to the solution 32 ml of aqueous sodium hydroxide solution IN, the mixture is stirred for 3 hours at room temperature. Hydrochloric acid (16 ml) is then added to the reaction mixture followed by concentration in vacuo. The residue is purified by silica gel column chromatography (250 ml, chloroform: methanol: acetic acid = 20: 1: 0.5) to give the compound (32D-B) (3.13 g, yield: 66. 9%). 'H-NMR (200 MHz, CD30D) d: 2.72 (3H, t, J = 6.5 Hz), 3.33 (3H, t, J = 6.5 Hz), 7.59 (1H, m), 8.42 (1H, m), 8.73 (1H, m), 9.14 (1H, m). MS (BAR, POS) m / z: 180 (M + H) + (3) Preparation of 4-oxo-4- (3-pyridyl) -3- (1-piperidyl) methylbutyric acid (compound 32D-C) Piperidine (140 mg, 1.64 mmol) and 37% formalin (0.133 ml) are added, 1.64 mmol) to the compound (32D-B) (246 mg, 1.37 mmol). The mixture is stirred at 100 ° C for 2 hours. 1.8 g of silica gel is added to the reaction solution. After concentration, the residue is purified by silica gel column chromatography (30 ml, chloroform: methanol: acetic acid = 10: 1: 0.5 to 10: 5: 3) to give the compound (32D-C) (300 mg, yield: 79%). 'H-NMR (200 MHz, CDC13) d: 1.45-1.80 (6H, m), 2.30 -3.15 (8H, m), 4.28 (1H, m), 7.46 (1H, dd, J = 4.7 Hz, 8.0 Hz ), 8.00 (1H, broad s), 8.37 (1H, dt, J = 2.0 Hz, 8.0 Hz), 78 (1H, dd, J = 1.6 Hz, J = 4.8 Hz), 9.28 (1H, d, J = 1.6 Hz) (4) Preparation of 3- [(2R) - (2-acetylamino-2-methoxycarbonyl) ethylthiol methyl-4-oxo-4- (3-pyridyl) -butyric acid (compound 32D) N-acetyl-L-cysteine methyl ester is added (96.2 mg, 0.54 mmol) to a solution of the compound (32D-C) (150 mL, 0.54 mmol) in ethanol (3 mL). The mixture is refluxed for 2 hours. The reaction mixture is concentrated. The residue is purified by silica gel column chromatography (30 ml, chloroform: methanol: acetic acid = 20: 1: 0.5) to provide the compound (32D) (89 mg, yield: 44.7%). 'H-NMR (200 MHz, CDC13) d: 1.98 (1.5H, s), 2.01 (1.5H, s), 2.70 (2H, m), 2.93 (4H, m), 3.68 (1.5H, s), 3.71 (1.5H, s), 4.06 (1H, m), 4.79 (1H, m), 6.80 (1H, m), 7.20 (1H, m, NH), 7.49 (1H, m), 8.35 (1H, m), 8.75 (1H, d, J = 3.9 Hz), 9.24 (1H, s), 1048 (1H, broad s). MS (BAR, POS) m / z 369 (M + H) + Example 33 Preparation of the acid 4- [(2R) -. { (2-acetylamino-2-carboxy) -ethylthio} 1 methyl-5-oxo-5-phenylpentanoic (compound 38D) (1) Preparation of 4- (1-piperazinyl) methyl-5-oxo-5-phenylpentanoic acid (compound 38D-A) 4-Benzoylbutyric acid (1000.9 mg, 5.21 mmol) is suspended in an aqueous solution of formalin (507 mg, 6.25 mmol) and piperidine (532 mg, 6.25 mmol). The reaction is carried out at 100 ° C for 3 and a half hours. Piperidine is added to it (517 mg, 6.07 mmol) and the mixture is heated at 100 ° C for an additional 3 hours. After cooling to room temperature air, the reaction mixture is concentrated in vacuo. The residue is purified by silica gel column chromatography (100 ml, dichloromethane: methanol = 10: 1 to 5: 1) to provide the compound (38D-A) (1500.8 mg, yield: 99%). 'H-NMR (200 MHz, CDC13) d: 1.2-1.8 (8H, m), 2.10 (1H, m), 2.42 (1H, m), 2.5-3.0 (4H, m), 3.16 (1H, dd, J = 2.0 Hz, 12.7 Hz), 3.38 (4H, m), 3.16 (1H, dd, J = 2.0 Hz, 12.7 Hz), 3.38 (1H, dd, J = 8.1 Hz, 12.5 Hz), 4.37 (1H, m), 7.2-7.4 (2H, m), 7.46 (1H, t, J = 7.4 Hz), 8.41 (2H, d, J = 7.2 Hz), 9.30 (1H, broad). MS (BAR, POS) m / z: 290 (M + H) + (2) Preparation of 4 - [(2R) - acid. { (2-acetylamino-2-carboxy) et ilt io} ] ethyl-5-oxo-5-f-enylpentanoic (compound 38D) The compound (38D-A) (576.0 mg, 1.99 mmol) and (R) -N-acetylcysteine (324.7 mg, 1.99 mmol) is dissolved in ethanol (5%). ml). The solution is refluxed for 4 hours. After cooling in air, the mixture is concentrated in vacuo. The residue is purified by silica gel column chromatography (100 ml, chloroform: methanol = 10: 1 to 3: 1) to provide the compound (38D) (417.4 mg, yield: 57%). 'H-NMR (200 MHz, DMS0-d6) d: 1.7-2.0 (2H, m), 1.83 (3H, d, J = 2 Hz), 2.20 (2H, t, J = 7.3 Hz), 2.6-3.0 (4H, m), 3.86 (1H, m), 4.33 (1H, dt, J = 4.8 Hz, 7.4 Hz), 7.5-7.7 (3H, m), 8.00 (2H, dd, J = 7.0 Hz, 2.2 Hz ), 8.09 (1H, d, J = 7.3 Hz).

MS (BAR, NEG) m / z: 366 (M-H) + Example 34 Preparation of (1R.2S) -2- [N- (Pantoyl-alanylamido) ethylthiol methyl-3-oxo-1-cyclopentanecarboxylic acid (compound IE) One aliquot of 100 ml of seed culture medium (2.0% glycerin, 1.0% glucose, 0.5% soybean arina, 0.3% peptone, 0.5% yeast extract, 0.2% calico carbonate, 0.05% dipotassium phosphate and sulfate 0.05% magnesium, pH 7.0) are loaded in an Erlenmeyer flask with stirrer ßar, - «» -st »^^^"?? ai * ~ - - * "** t: ?? ~ ^ ¡ii '* > ^ -fe-rotary of a volume of 500 ml and sterilized at 120 ° C for 20 minutes in an autoclave. A platinum loop of strain NA32176 (FERM P-16372) is inoculated into the medium and cultured at 27 ° C for 2 days at 220 rpm. In the main crop, an aliquot of 100 ml of culture medium (glucose 1.0%, 4.0% starch syrup, 1.0% corn infusion liquor, 0.2% yeast extract, 1.0% gluten flour, iron sulfate heptahydrate 0.00011%, copper sulfate pentahydrate 0.00064% , zinc sulfate heptahydratate 0.00015%, manganese chloride tetrahydrate 0.00079%, cobalt chloride 0.0001% and calcium carbonate 0.2%; pH 7.0) in an Erlenmeyer flask with a rotary agitator of a volume of 500 ml, which has been sterilized at 120 ° C for 20 minutes in an autoclave. 1 ml of the above seed culture broth is inoculated to the main medium loaded in the flask and cultured at 27 ° C for 2 days, at 220 rpm. The cultured broth (10 1) is filtered in a conventional manner to separate the filtrate and the mycelial cake. After the pH is adjusted to 8 with 4N sodium hydroxide, the filtrate is applied to a DIAION HP-20 column (11), and then washed. The elution is carried out by a linear gradient from water (2 1) to 80% methanol (2 1). After the methanol is removed, the pH of the eluted reaction is adjusted to 2 with IN hydrochloric acid. Follow the extraction with n-butanol.

The n-butanol layer is concentrated in vacuo. The residue (491 mg) is applied to column chromatography of Sephadex LH-20 (fai 3.5 x 90 cm, mobile faso: methanol). 267 mg of the active fraction obtained in this manner are dissolved in a mixture of ethyl acetate-water (11). The solution is then subjected to liquid-liquid centrifugal liquid chromatography (250 ml volume, 1500 rpm, flow rate: 3 ml / min - the lower phase of the mixture is pre-seeded to operate as the fixed phase). After washing the upper phase of the mixture with the liquid, the active fraction is eluted inversely by the lower phase to provide the 16 mg of the raw or untreated active substance. The crude substance is purified by Sephadex LH-20 column chromatography (fai 1.8 x 85 cm, mobile phase: methanol) to provide 13 mg of NA32176A (compound E). Appearance, molecular weight, solubility, Rf value by ODS thin layer chromatography, UV absorption spectrum, IR absorption spectrum, 'H-NMR spectrum and 13C-NMR spectrum of NA32176A (compound IE) purified as indicated above is have determined. It is found that the physico-chemical properties of NA32176A (compound IE) are as described above.

Example 35 I? S Preparation of 4-oxo-4-phenyl-3- (1-piperidyl) methylbutyric acid (compound 1F) The compound (1F) can be prepared by a known process, for example as described in J. Chem. Soc. (C), 2308 (1967).

Example 36 Preparation of 4- (4-methyl-phenyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (compound 2F) Piperidine (1027 mg, 12.07 mmol) and 37% aqueous formaldehyde solution (0.98 mL, 12.07 mmol) were added 4- (4-methylphenyl) -4-oxobutyric acid (2320 mg, 12.07 mmol). The mixture is heated until it becomes homogeneous. The reaction solution is then stirred at room temperature for 15 hours and concentrated in vacuo. The residue is purified by chromatography on a silica gel column (chloroform: methanol = : 1 to 10: 1) to provide the compound (2F) (745 mg, yield: 22.6%). 'H-NMR (60 MHz, CDC13) d: 1.66-2.36 (6H,), 2.50- 3.05 (2H,), 2.85 (3H, s), 3.60 (2H, m), 4.70 (1H, m), 7.61 (2H, d, J = 9.1 Hz), 8.30 (2H, d, J = 9.1 Hz), 10.3 (1H, 25 s broad). as'_ EM (BAR, POS) m / z: 274 (M + H) + Example 37 Preparation of 4- (4-methoxyphenyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (compound 3F) Piperidine (851 mg, 10 mmol) and 37% aqueous formaldehyde solution (0.81 ml, 10 mmol) are added to the 4- (4-methoxyphenyl) -4-oxobutyric acid (2080 mg, 10 mmol). The mixture is heated to become homogeneous. The reaction solution is stirred at room temperature for 3 hours and concentrated in vacuo. The residue is purified by silica gel column chromatography (250 ml, chloroform: methanol = 20: 1 to 15 10: 1) to give the compound (3F) (552 mg, yield: 19%). 'H-NMR (60 MHz, CDC13) d: 1.60-2.48 (6H, m), 2.66-3.30 (2H, m), 3.16-3.50 (4H, m), 3.70 (3H, m), 4.33 (3H, m), 4.80 (1H, m), 7.35 (2H, d, J = 9.5 Hz), 8.50 (2H, d, J = 9.5 Hz), 20 11.40 (1H, broad s). MS (BAR, POS) m / z: 290 (M + H) + Example 38 Preparation of 4-oxo-4-phenyl-3- (1-pyrrolidinyl! Methylbutyric acid (compound 4F) Pyrrolidine (1020 mg, 14.34 mmol) and 1.16 ml of a 37% formaldehyde aqueous solution are added to 4-oxo-4-phenylbutyric acid (2555 mg, 14.34 mmol). The mixture is heated to become homogeneous. The reaction solution is stirred at room temperature for 10 hours and concentrated in vacuo. Part of the residue (920 mg) is purified by silica gel column chromatography (90 ml, chloroform: methanol = 5: 1 to 2: 1) to provide the compound (4F) (372 mg, yield: 40%). 'H-NMR (60 MHz, CD30D) d: 2.17 (4H, m), 2.64 (2H, m), 3.30-3.72 (6H, m), 4.33 (1H, m), 7.60 (3H, m), 8.12 (2H, m). MS (BAR, POS) m / z: 262 (M + H) + Example 39 Preparation of 3- (4-morpholinyl) methyl-4-oxo-4-phenylbutyric acid (compound 5F) Morpholine (3891 mg, 4.47 mmol) and an aqueous solution of 37% formaldehyde (0.37 g, 4.47 mmol) were added to 4-oxo-4-phenylbutyric acid (797 mg, 4.47 mmol). The mixture is heated to become homogeneous. The reaction solution is stirred at room temperature for 15 hours and concentrated in vacuo. The residue is purified by silica gel column chromatography (200 ml, chloroform: methanol = 10: 1 to 2: 1) to give the compound (5F) (510 mg, yield: 41%). 'H-NMR (200 MHz, CD3CD) d: 2.40-3.08 (8H, m), 3.69 (4H, t, J = 4.68 Hz), 4.21 (1H, m), 7.50 (3H, m), 8.00 (2H, m), 10.40 (1H, broad s). MS (BAR, POS) m / z: 278 (M + H) + Example 40 Preparation of the acid 3 -. { 1- (4-methylpiperazinyl)} methyl-4-oxo-4-phenylbutyric (compound 6F) Add 1-meth? Piperazine (349 mg, 3.51 mmol) and an aqueous solution of 37% formaldehyde (0.29 mL, 3.51 mmol) to 4-oxo-4-phenylbutyric acid (627 mg, 3.51 mmol). The mixture is heated to become homogeneous. The reaction solution is stirred at room temperature for 15 hours and concentrated in vacuo. The residue is purified by silica gel column chromatography (90 ml, butanol: acetic acid: water = 20: 1: 1) and Sephadex LH-20 (250 ml, 80% hydrated methanol) to provide the compound (6F) (251 mg, yield: 24.6%).

'H-NMR (60 MHz, CDC13) 2.50-3.60 (12H, m), 2.84 (3H, s), 4.50 (1H, m), 7.80 (3H, m), 8.30 (2H, m), 12.16 (1H , s broad). MS (BAR, POS) m / z: 291 (M + H) + Example 41 Preparation of 3- (diethylamino) methyl-4-oxo-4-phenylbutyric acid (compound 7F) Diethylamine (300 mg, 4.10 mmol) and an aqueous solution of 37% formaldehyde (0.33 ml) are added to 4-oxo-4-phenylbutyric acid (730 mg, 4.10 mmol). The mixture is heated to become homogeneous. The reaction solution is stirred at room temperature for 16 hours and concentrated in vacuo. The residue is purified by silica gel column chromatography (90 ml, chloroform: methanol = 10: 1 to 5: 1) to give the compound (7F) (312 mg, yield: 28.9%). 'H-NMR (60 MHz, CDC13) d: 1.90 (6H, t, J = 6.8 Hz), 3.06-4.00 (8H, m), 4.95 (1H, m), 8.20 (3H, m), 8.72 (2H , m), 11.70 (1H, broad s). MS (BAR, POS) m / z: 264 (M + H) + Example 42 Preparation of the acid (IR, 2R) -3-oxo-2- (1-piperidyl) methyl-1-cyclopentanecarboxylic acid (compound 8F) The acid is dissolved (IR, 2S) -2- [(2RS) - (2, 3-0-isopropylidene) propylsulfonyl] methyl-3-oxo-1-cyclopentanecarboxylic acid (205 mg, 0.614 mmol) in acetone (3 ml). To the solution, piperidine (55 mg, 0.64 mmol), methanol (2 ml) and sodium hydroxide IN (0.45 ml) are added successively. The mixture is stirred at room temperature for 20 hours. The reaction solution is concentrated in vacuo. The residue is purified by Sephadex LH-20 (250 ml, 80% hydrated methanol) to provide the compound (8F) (75 mg, yield: 52%). MS (BAR, POS) m / z: 226 (M + H) + Example 43 Preparation of the acid 4-oxo-4- (3-pyridyl) -3- (1-piperidyl) methylbutyric acid (compound 12F) (1) Preparation of methyl 4-oxo-4- (3-pyridyl) butyrate (compound 12F-A) Under a nitrogen atmosphere, a solution of 3-pyridinecarboxyaldehyde (10.7 g, 100 mmol) in anhydrous dimethylformamide (20 ml) is added dropwise to a solution of sodium cyanide (2.44 g, 50 mmol) at 30 ° C in dimethylformamide. anhydrous (80 ml) for 30 minutes. After stirring for 30 minutes, a solution of methyl acrylate (8.6 g, 100 mmol) in anhydrous dimethylformamide (80 ml) was added dropwise over 1 hour followed by stirring for 3 hours at 30 ° C. Acetic acid (0.66 ml) and water (30 ml) are added to the reaction solution. After stirring for 10 minutes, the mixture is concentrated in vacuo. Water (360 ml) and chloroform (300 ml x 3) are added to the residue for separation. The resulting organic phase is washed with a saturated aqueous solution of sodium chloride (300 ml), dried over anhydrous sodium sulfate and concentrated by evaporation. The residue is purified by silica gel column chromatography (650 mL, hexane: ethyl acetate = 1: 1 to 1: 2) to provide the compound (12F-A) (7.87 g, yield: 40.7%). (2) Preparation of 4-oxo-4- (3-pyridyl) butyric acid (compound 12F-B) The compound (12F-A) (5.04 g, 26.11 mmol) was dissolved in methanol (60 ml). After 32 ml of an aqueous solution of IN sodium hydroxide has been added to the solution, the mixture is stirred for 3 hours at room temperature. Then 16 ml of 2N hydrochloric acid is added to the reaction mixture, followed by concentration in vacuo. The residue is purified by silica gel column chromatography (250 ml, chloroform: methanol: acetic acid = 20: 1: 0.5) to give the compound (12F-B) (3.13 g, yield: 66.9%). 'H-NMR (200 MHz, CD30D) d: 2.72 (3H, t, J = 6.5 Hz), 3.33 (3H, t, J = 6.5 Hz), 7.59 (1H, m), 8.42 (1H, m), 8.73 (1H, m), 9.14 (1H, m). MS (BAR, POS) m / z: 180 (M + H) + (3) Preparation of 4-oxo-4- (3-pyridyl) -3- (1-piperidyl) methylbutyric acid (compound 12F) Pipepdine (140 mg, 1.64 mmol) and 37% formalin (0.133 ml, 1.64 mmol) were added to the compound (12F-B) (246 mg, 1.37 mmol). The mixture is stirred at 100 ° C for 2 hours. 1.8 g of silica gel is added to the reaction solution. After concentration, the residue is purified by silica gel column chromatography (30 ml, chloroform: methanol: acetic acid = 10: 1: 0.5 to 10: 5: 3) to provide the compound (12F) (300 mg , yield: 79%). 'H-NMR (200 MHz, CDC13) d: 1.45-1.80 (6H, m), 2.30-3.15 (8H, m), 4.28 (1H, m), 7.46 (1H, dd, J = 4.7 Hz, 8.0 Hz ), 8.00 (1H, broad s), 8.37 (1H, dt, J = 2.0 Hz, 8.0 Hz), 8.78 (1H, dd, J = 1.6 Hz, J-4.8 Hz), 9.28 (1H, d, J = 1.6 Hz). MS (BAR, POS) m / z: 180 (M + H) + Example 44 Preparation of 1-acid 4- (2-furyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (compound 26F-A) (1) Preparation of methyl 4- (2-furyl) -4-oxobutyrate (compound 26F-A) After 3-benzyl-5- (2-hydroxyethyl) -4-methylthiazolium chloride (1.0 g, 4 mmol) and triethylamine (2.02 g, 20 mmol) are added to a furfural solution (4.8 g, 50 mmol) in absolute ethanol (30 ml). The mixture is stirred at room temperature for 40 minutes. Methyl methacrylate (5.0 g, 50 mmol) is further added to the mixture followed by heating at reflux for 7 hours. The reaction solution is concentrated in vacuo. The residue obtained is purified by silica gel column chromatography (600 ml, hexane: ethyl acetate = 2: 1) to give the compound (26F-A) (3430 mg, yield: 37.6%). 'H-NMR (200 MHzl CDC13) 2.74 (2H, t, J = 6.8 Hz), 3.18 (2H, t, J = 6.8 Hz), 6.54 (1H, dd, J = 1.7 Hz, 3.6 Hz), 7.23 (1H, dd, J = 0.7 Hz, 3.6 Hz), 7.59 (1H, dd, J = 0.7 Hz, 1.7 Hz). MS (BAR, POS) m / z: 180 (M + H) + (2) Preparation of 4- (2-furyl) -4-oxobutyric acid (compound 26F-B) & ^ & Tgmnsr .. * r ^ ¡'- «?: ~ .s? To a solution of the compound (26F-A) (1820 mg, 10 mmol) in methanol (20 ml) is added 10.5 ml of an aqueous solution of sodium hydroxide IN. The mixture is stirred at room temperature for 3 hours. After concentration in vacuo, water (30 ml) and ethyl acetate (30 ml) are added to the residue for separation. The pH of the aqueous phase is adjusted to 3.0 with an aqueous 2N hydrochloric acid solution followed by extraction with ethyl acetate (30 ml x 2). The organic phase is washed with 50 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated vacuo to give the compound (26F-B) (1445 mg, yield: 86%). 'H-NMR (200 MHz, CDC13) d: 2.77 (2H, t, J = 6.6 Hz), 3.17 (2H, t, J = 6.6 Hz), 6.55 (1H, dd, J = 1.7 Hz, 3.7 Hz) , 7.23 (1H, dd, J = 0.7 Hz, 3.6 Hz), 7.59 (1H, dd, J = 0.7 Hz, 1.7 Hz). MS (BAR, POS) M / Z: 168 (M + H) + 3) Preparation of 4- (2-furyl) -4-oxo-3- (1-piperidyl) methylbutyric acid (compound 26F) Piperidine (797 mg, 9.36 mmol) and 37% formalma (0.76 ml, 9.36 mmol) were added to the compound (26F-B) (1431 mg8.51 mmole). The mixture is stirred at room temperature for 4 days. 4.5 g of silica gel is added to the reaction solution. After being concentrated in vacuo, the residue is purified by silica gel column chromatography (100 ml, chloroform: methanol: acetic acid = 10: 1: 0.5 to 3: 1: 0.3) to provide the compound (26F) (1325 mg, yield: 62.5%). 'H-NMR (200 MHz, CDC13) d: 1.56 (2H, m), 1.79 (4H, m), 2.48 (1H, dd, J = 10.7 Hz, 15.5 Hz), 2.82 (5H, m), 3.16 ( 2H, d, J = 6.2), 4.08 (lH, m), 6.60 (1H, dd, J = 1.7 Hz, 3.6 Hz), 7.49 (1H, d, J = 3.6 Hz), 7.66 (1H, d, J = 1.6 Hz), 10.7 Hz (1H, broad s). MS (BAR, NEG) m / z: 264 (M-H) - Example 45 Preparation of 3- (1-piperidyl) methyl-4-oxo-4- (4'-trifluoromethylphenyl) butyric acid (compound 9F) Preparation of 4 '- (trifluoromethyl) cinnamic acid (Compound 9F-A) A mixture of 4 '- (trifluoromethyl) acetophenone (2500.5 mg, 13.29 mmol) and glyoxylic acid monohydrate (1223.3 mg, 13.29 mmol) is reacted at 95 ° C for 1 hour while being sucked through the aspirator. Additional glyoxylic acid monohydrate (439.5 mg, 477 mole) is added to the system and the mixture is reacted at 95 ° C for 2 hours while suctioning through a vacuum cleaner. After cooling to room temperature, 20 ml of 5% potassium carbonate is added to the reaction solution. The mixture is extracted twice with ethyl acetate. The aqueous layer is adjusted to pH 1 with 4N hydrochloric acid and then extracted with ethyl acetate twice. The extract is washed with water and then with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is dissolved in 10 ml of acid in acetic acid and 0.5 ml of concentrated hydrochloric acid are added to the solution. The mixture is refluxed for 7 hours. The reaction solution is concentrated in vacuo. The residue is dissolved in acid in ethyl acetate. The solution is washed with water and then with a saturated solution of aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is recrystallized from hexane-ethyl acetate to provide the compound (9F-A) (1554.5 mg, yield: 48%). 'H-NMR (60 MHz, CD30D) d: 6.93 (1H, d, J = 15 Hz), 7.83 (2H, d, J = 10 Hz), 8.00 (1H, d, J = 15 Hz), 8.14 ( 2H, d, J = 10 Hz) (2! Preparation of 4- (4 '- (trifluoromethylphenylbutyric acid (compound 9F-B) The compound (9F-A) (1036.9 mg, 4.25 mmol) is dissolved in acetic acid (9 ml) and water (2 ml). Zinc powders (320.1 mg, 4.89 mmoles) are added to the solution. The mixture is stirred at room temperature for 4 hours. After filtering through celite, the filtrate is concentrated in vacuo. The residue is suspended in ethyl acetate and purified to provide the compound (9F-B) (1111.0 mg, 100%). 'H-NMR (200 MHz, DMSO-d6) d: 3.22 (2H, t, J = 6.3 Hz), 3.37 (broad), 7.88 (2H, d, J = 8.3 Hz), 8.15 (2H, d, J = 8.3 Hz). (3) Preparation of 3- (1-piperidyl) methyl-4-oxo-4- (4'-trifluoromethylphenyl) butyric acid (compound 9F) The compound (9F-B) (1005.7 mg, 4.08 mmol) is dissolved in dimethyl sulfoxide (10 ml). An aqueous solution of formalin (507 mg, 6.25 mmole) and piperidine (532 mg, 6.25 mmole) are added to the solution. The mixture is reacted at 100 ° C for 24 hours. After cooling with ice, the precipitates are separated by filtration. The filtrate is separated with water and ethyl acetate. The aqueous phase is then extracted with ethyl acetate, and the combined organic layers are washed with a saturated aqueous solution of sodium chloride and concentrated in vacuo. The residue is purified by silica gel column chromatography (200 ml, chloroform: methanol = 5: 1 to 1: 2) to give the compound (9F) (312.5 mg, yield: 22%). 'H-NMR (200 MHz, DMSO-d6) d: 1.4-1.0 (6H, m), 2.36 (1H, dd, J = 10.1 Hz, 15.2 Hz), 2.70 (1H, dd, J = 15.3 Hz, 2.4 Hz), 2.7-3.0 (4H, m), 3.26 (2H, d, J = .2 Hz), 4.40 (1H, m), 7.78 (2H, d, J = 8.5 Hz), 8.24 (2H, d, J = 8.1 Hz). EM (BAR, NEG) m / z: 343 (M) Example 46 Preparation of 2-methyl-4-oxo-4-phenyl-3- (1-piperazinyl) methylbutyric acid (compound 41F) 2-Methyl-4-oxo-4-phenylbutyric acid (1000.5 mg, . 21 mmol) is suspended in an aqueous solution of formalin (507 mg, 6.25 mmol) and piperidine (532 mg, 6.25 mmol). Ethanol (6 ml) is additionally added to the suspension. The reaction is carried out 100 ° C for 40 minutes. The crystals that are obtained by filtration with heating dried to provide the compound (41F) (529.2 mg, yield: 35%). MS (BAR, POS) m / z: 290 (M + H) + Example 47 Preparation of 4- (1-piperazinyl) methyl-5-oxo-5-phenylpentanoic acid (compound 42F) 4-Benzoylbutyric acid (1000.9 mg, 5.21-25 mmol) is suspended in an aqueous solution of formalin (507 mg, 6.25 mmol) and piperidine (532 mg, 6.25 mmol). The reaction is carried out at 100 ° C for 3 and a half hours. Piperidine (517 mg, 6.07 mmol) is added thereto and the mixture is heated at 100 ° C for an additional 3 hours. After cooling the air to room temperature, the reaction mixture is concentrated in vacuo. The residue is purified by silica gel column chromatography (100 ml, dichloromethane: L = 10: 1 to 5: 1) to provide the compound (42F) (1500.8 mg, yield: 99%). 'H-NMR (200 MHz, CDC13) d: 1.2-1.8 (8H, m), 2.10 (1H, m), 2.42 (1H, m), 2.5-3.0 (4H, m), 3.16 (1H, dd, J = 2.0 Hz, 12. 7 Hz), 3.38 (1H, dd, J = 8.1 Hz, 12.5 Hz), 4.37 (1H, m), 7.2- 7.4 (2H, m), 7.46 (1H, t, J = 7.4 Hz), 8.41 (2H , d, J = 7.2 Hz), 9. 30 (1H, broad). MS (BAR, POS) m / z: 290 (M + H) + Test example 1 Effect of neurite-like neurite extension of the compounds of this invention on PC12 cells The effect of the compounds of the invention is examined by a modification of the method of Green et al., Ann.

Rev. Neurosci., 3, 353, 1980, and evaluated in terms of morphological change of PC12 cells and a level of change. That is, PC12 cells are inoculated into Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and 10% equine serum at approximately 100,000 cells / ml. The cells are incubated at 37 ° C overnight in C02 5% using multiple 96-well plates coated with collagen. The morphological change of the cells is observed microscopically a few days after the test compound has been added to each well, under these conditions. Table 2 below shows the minimum effective dose (MDE, g / ml) of each compound on PC12 cells that cause extension of neurites similar to neurons.

Table 2 Minimum effective dose to cause neurite-like neurite extension on PC12 cells. soSá » MLAiBttMWM- > . ** & Industrial Applicability The compounds of the present invention or the pharmacologically acceptable salts thereof show a potent neuron differentiation accelerating activity. Pharmaceutical compositions comprising these pharmacologically acceptable compounds or salts thereof are therefore useful as accelerators of neuron differentiation and are effectively applicable as medicaments for the treatment of disorders of the central nervous system or of the nervous system in general.

Claims

1. A cyclopentanone derivative, represented by the formula [ÍA]: wherein: XA is O, S, SO, S02 or NH; YA is a linear or branched aliphatic hydrocarbon group having from 1 to 20 carbon atoms, which may be substituted or unsubstituted or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms. carbon; each of Z1A, Z2A and Z3A, which may be the same or different and independently represent carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived from the same, amino or a group derived from it, sulfonate or a derivative thereof, phosphate or a group derived therefrom, a monocyclic heteroaryl, a halogen or a flB hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon or ring Aromatic heterocyclic; and Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen, with the The proviso is that when Z2A and Z3A are both hydrogen, Z1A is hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a monocyclic aromatic heterocyclic ring, a halogen or hydrogen, and YA is an aliphatic hydrocarbon group. straight or branched chain substituted 15 or unsubstituted having 1 to 6 carbon atoms; with the proviso that subparagraphs (1) to (7) are excluded: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl, and Z3A is methoxycarbonyl, 20 (2) when Z1A and Z2A is hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or O, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) Xs is O, Z1A is hydroxy or a group derived from the same, Z2A is hydrogen and Z3A is amino or a group derived from the same; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen; or a pharmacologically acceptable salt thereof; a 2,3-disubstituted cyclopentanone derivative of the formula [IB]: wherein: XB is 0, S, S0, S02 or NH; YB is: an unsubstituted or substituted straight or branched chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms, a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: less a hydrogen is substituted with C0 1 (wherein W1 is an unsubstituted or substituted aromatic heterocyclic ring or a saturated heterocyclic ring) and at least one hydrogen may be further substituted with an amino derivative group; or at least one hydrogen is substituted with NHC0V1 (wherein VI is an alkyl having 2 to 5 carbon atoms containing 4 to 11 halogen atoms) and at least one hydrogen may further be substituted with carboxy or a group derived therefrom; or at least one hydrogen is substituted with a substituted or unsubstituted monocyclic aromatic heterocyclic ring and at least one hydrogen may be further substituted with amino or a group derived therefrom; or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms; ZB is carboxy or a group derived therefrom, sulfonate or a group derived therefrom, phosphate or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy, ORÍ (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NHCOR 2 (wherein R 2 is an unsubstituted or substituted alkyl having 1 to 4) carbon atoms), NHS02R2 '(wherein R2' is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or phenyl), an aromatic heterocyclic ring, a halogen or hydrogen; or a pharmacologically acceptable salt thereof; a cyclopentanone derivative of formula [IC]: wherein: a ring A has a double bond conjugated with oxo; Xc is O, S, SO, S02 or NH; Xc is a substituted or unsubstituted aliphatic hydrocarbon group having from 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms; each of Zlc, Z2C and Z3C, which may be the same or different and independently represent carboxy or a group derived therefrom, hydroxy or a group derived therefrom, amino or a group derived therefrom, an unsubstituted or substituted alkyl or an alkenyl having from 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen atom or hydrogen; with the proviso that when Xc is O or NH, Zlc and Z3C are not hydrogen and Z2C is not hydrogen or hydroxy or a group derived therefrom, or a pharmacologically acceptable salt thereof; a ketone derivative of formula [ID]: wherein: AD is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms, an unsubstituted or substituted aromatic hydrocarbon, a heterocyclic ring or a saturated heterocyclic ring; BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; or 25 AD and BD combine together to form a ring »• *. unsubstituted or substituted cycloalkan-1-one having from 3 to 7 carbon atoms (except for 5 carbon atoms); XD is O, S, SO, S02 or NH; YD is a substituted or unsubstituted aliphatic hydrocarbon group having from 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or a monocyclic aromatic heterocyclic ring having from 3 to 6 carbon atoms; ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl group having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derivative thereof or phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; with the proviso that, when AD and BD are combined together to form a cyclobutane ring, the following items (1) to (4) are excluded: (1) XD is O, YD is methyl, n-octyl or n- hexadecyl and 20 ZD is methoxycarbonyl; (2) XD is 0, YD is benzyl and ZD is benzyloxymethyl; (3) XD is O, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is 0, YD is trityl and ZD is trityloxymethyl or when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy; or a pharmacologically acceptable salt thereof; a compound of formula [ÍE]: or a pharmacologically acceptable salt thereof; or a β-disubstituted aminoketone derivative of the formula [1F]: where R & ias? káÉ = AF is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms or an unsubstituted or substituted aromatic hydrocarbon ring, an aromatic heterocyclic ring or a saturated heterocyclic ring; BF is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms; or AF and Bp combine together to form an unsubstituted or substituted cycloalkan-1-one ring having from 3 to 7 carbon atoms or to form a cycloalkan-1-one ring having from 3 to 7 carbon atoms and fused with an aromatic hydrocarbon or an aromatic heterocyclic ring; each of XF and YF is an unsubstituted or substituted straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms or XF and YF are linked together directly or via a heteroatom to form an unsubstituted heterocyclic ring or replaced; ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived from the same, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen; with the proviso that when AF is an unsubstituted benzene ring we exclude those where BF is hydrogen, XF and YF are linked together directly to form a piperidine ring and ZF is carboxy; or a pharmacologically acceptable salt thereof.

2. A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: XA is S, 0, S or SO; YA is a straight or branched chain aliphatic hydrocarbon group having from 1 to 20 carbon atoms (wherein at least one hydrogen atom is substituted with carboxy or a group derived therefrom or amino or a group derived therefrom); each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom , amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon or an aromatic heterocyclic ring; and Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen.

3. A cyclopentanone derivative of the formula [IA] or a pharmacologically acceptable salt thereof, as described in claim 2, wherein: YA is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein; at least one hydrogen atom is substituted with carboxy, C00R1 (wherein R1 is a substituted or unsubstituted alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms), COW1 (wherein W1 is an unsubstituted heterocyclic ring) or substituted with carboxy or a group derived therefrom) or NR2R3 (wherein each of R2 and R3 which may be the same or different independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy, C00R4 (wherein R4 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6 which may independently be different or the same, represent hydrogen or a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is unsubstituted or substituted alkyl) having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9 which may be the same 0 differently and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein RIO is hydrogen, an alkyl not substituted or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), chlorine, fluoro or hydrogen; or Z2A and Z3A combine together to form a substituted or unsubstituted aromatic hydrocarbon; and Z1A is carboxy, C00R4 (wherein R4 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6 which may be independently the same or different, represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9, which independently can be the same or different represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), chlorine, fluoro or hydrogen.

4. A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, as described in claim 3, wherein: XA is S; YA is a straight chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: at least two hydrogen atoms are substituted with any carboxy, C00R1 '(where R1' is an alkyl, an alkenyl or alkynyl having 1 to 4 carbon atoms), COW2 (wherein W2 is a saturated heterocyclic ring unsubstituted or substituted with COOR11 (wherein Rll is an alkyl having 1 to 4 carbon atoms) or NHCOR12 (wherein R12 is an alkyl having 1 to 4 carbon atoms), each of Z1A, Z2A and Z3A, which may be the same or different and independently represent carboxy, C00R4 '(wherein R4' is an alkyl having 1 to 4 carbon atoms), hydroxy, 0C0R13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CHO2R10 '(wherein RIO' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen; or Z2A and Z3A combine together to form a benzene ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms, an alkyloxy having 1 to 4 carbon atoms, nitro, trifluoromethyl or halogen; and Z1A is carboxy, C00R4 '(wherein R4' is an alkyl having 1 to 4 carbon atoms), hydroxy, 0C0R13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CH2OR10 '( wherein RIO 'is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen.

5. A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, as described in claim 4, wherein: XA is S; YA is a straight chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms, wherein: a hydrogen is substituted with carboxy, methoxycarbonyl, COW3 (wherein W3 is a pyrrolidine, piperidine, azetidine, morpholine, or piperazine ring) which may be unsubstituted or substituted with methoxycarbonyl) and the other hydrogen is substituted with acetylamino; each of Z1A, Z2A and Z3A which may be the same or different and independently represent carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen; or Z2A and Z3A combine together to form an unsubstituted benzene ring; and Z1A is carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen.

6. A cyclopentanone derivative of formula [IA] or a pharmacologically acceptable salt thereof, as described in claim 5, wherein the cyclopentanone derivative is selected from the group consisting of: (I) XA is S, YA is 2-acetylammo-2-carboxyethyl, Z1A and Z3A are hydrogen and Z2A is carboxy; (II) XA is S, YA is 2-acetylamino-2-methoxycarbonylethyl, Z1A and Z3A are hydrogen and Z2A is carboxy; (III) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z1A and Z3A are hydrogen and Z2A is hydroxy; (IV) XA is S, YA is 2-acetylammo-3-oxo-3-. { 1- (2-methoxycarbonyl) pyrrolidinyl} propyl, Z1A and Z3A are hydrogen and Z2A is hydroxy; (V) XA is 2-acetylamino-2-methoxycarbonylethyl, Z2A and Z3A combine together to form an unsubstituted benzene ring and Z1A is carboxy; and (VI) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z2A and Z3A combine together to form an unsubstituted benzene ring and Z1A is carboxy.

7. A 2,3-di-substituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: XB is S, O or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms (wherein at least one hydrogen may be optionally substituted with carboxy or a derivative thereof or amino group) 5 or a group derived therefrom); and ZB is carboxy, C00R3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms); carbon) or CH2OCOR5 10 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms).

8. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 7, wherein: XB is S; YB is a straight chain aliphatic hydrocarbon group having from 7 to 20 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR6 (wherein R6 is an alkyl, an alkenyl or an alkynyl which 20 has from 1 to 4 carbon atoms) or NR7R8 (wherein each of R7 and R8, which may be the same or different and independently represents hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl which has from 1 to 5 carbon atoms); and 25 ZB is carboxy, methoxycarbonyl, hydroxymethyl or - * »" •% "acetyloxymethyl

9. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 8, wherein: XB is S; YB is 11-acetylamino-11-carboxy-n-undecyl; and ZB is carboxy.

10. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: XB is S, O or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms wherein at least one hydrogen is substituted with COW2. { wherein W2 is a saturated heterocyclic ring unsubstituted or substituted by carboxy, a hydroxyalkyl having 1 to 4 carbon atoms, phenyl or C00R9 (wherein R9 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms )} and at least one other hydrogen is substituted with NRlORll (wherein each of RIO and Rll, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or a unsubstituted or substituted acyl having 1 to 5 carbon atoms); and ZB is carboxy, C00R3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms); carbon) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms).

11. A 2,3-disubstituted cyclopentanone derivative of the formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 10, wherein: YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein a hydrogen is substituted with COW3 (wherein W3 is a 1-azetidinyl, 1-piperidyl, 1-pyrrolidinyl, 1-piperazinyl, or 4-morpholinyl group, which may be unsubstituted or substituted by carboxy, methoxycarbonyl, -hydroxyethyl, phenyl or tert-butoxycarbonyl) and the other one of the hydrogens is substituted with NHC0R12 (wherein R12 is an alkyl having 1 to 4 carbon atoms)}; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxy.

12. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 11, wherein: XB is S; YB is 2-acetylamino-3-oxo-3- (1-pyrrolidinyl) propyl, 2-acetylamino-3-. { 1- (2-methoxycarbonyl) pyrrolidinyl-3-oxopropyl, 2-acetylamino-3-oxo-3- (1-piperidyl) propyl, 2-acetylamino-3- (4-morpholinyl) -3-oxopropyl, 2-acetylamino- 3- . { 1- (2-methoxycarbonyl) azetidinyl} -3-oxopropyl, 2-acetylamino-3-oxo-3- (1-pipera z ini 1) propyl, 2-ace t i 1 amino-3 - [1 -. { 4- (2-Hydroxyethyl) piperazinyl} ] -3-oxopropyl, 2-acetylamino-3-. { 1- (4-phenylpiperazinyl)} -3-oxopropyl or 2-acetylamino-3-. { 1- (4-tert-butoxycarbonylpiperazinyl)} -3-oxopropyl; and ZB is carboxy or methoxycarbonyl.

13. A 2,3-disubstituted cyclopentanone derivative of a formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: XB is S, O or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein at least one hydrogen is substituted with NHCOV1 (wherein VI is an alkyl having from 2 to 5 carbon atoms and contains from 4 to 11 halogen atoms) and at least one of the hydrogens can be further substituted with carboxy or COOR13 (wherein R13 is an unsubstituted or substituted alkyl, alkenyl or alkynyl having from 1 to 4 carbon atoms)}; Y ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted algeryl having from 1 to 4 carbon atoms ) or CH2OCOR5 (where R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms). A 2, 3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 13, wherein: YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein a hydrogen is substituted with NHCOV2 (wherein V2 is an alkyl having 2 to 5 carbon atoms and contains from 4 to 11 fluoro atoms) and the other one of the hydrogens is further substituted with carboxy or COOR13 '(in where R 13 'is an alkyl, alkenyl or alkynyl having from 1 to 4 carbon atoms)}; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl. 15. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 14, wherein:? TS YB is 2-carboxy-2- (pentafluoropropionyl) aminoethyl; Y ZB is carboxy or hydroxymethyl. 16. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: XB is S, 0 or SO; YB is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms. { wherein at least one hydrogen is substituted with an unsubstituted or substituted monocyclic aromatic heterocyclic ring and at least one of the hydrogens is further substituted with NR15R16 (wherein each of R15 and R16 which may be the same or different independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms)}; and ZB is carboxy, C00R3 (wherein R3 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms); carbon) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms). 17. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as described in claim 16, wherein:? .Q? S} YB is a straight chain aliphatic hydrocarbon group having from 1 to 4 carbon atoms. { wherein a hydrogen must be substituted with an unsubstituted or substituted pyridine ring with an alkyl having 1 to 4 carbon atoms or with 5-tetrazolyl, and the other one of the hydrogens can be further substituted with NHC0R17 (wherein R17 is an alkyl having 1 to 4 carbon atoms; and ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl 18. A 2,3-disubstituted cyclopentanone derivative of formula [IB] or a pharmacologically acceptable salt thereof, as it is described in claim 17, wherein: g TS YB is 3- (3-pyridyl) propyl, 3-. {3- (l-methylpyridinium iodide) J-propyl or 2-acetyl-amino-2- (5-tetrazolyl) ethyl) ZB is carboxy or methoxycarbonyl 19. A cyclopentanone derivative of the formula [C] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: ring A forms a conjugated oxo double bond together with the carbon atom bound to CH2-XC-YC; Xc is S, O or SO; Yc is a aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); and each of Zlc, Z2C and Z3C which may be the same or different and independently represents carboxy or a group derived therefrom, hydroxy or a group derived therefrom, amino or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having from 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 20. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 19, wherein: ring A forms a conjugated oxo double bond together with the carbon atom attached to CH2-XC -YC; Xc is S, 0 or SO; Y c is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR 1 (wherein R 1 is unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms) carbon), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted by carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 wherein each of R4 and R5 which may be the same or different and independently represents hydrogen, an alkyl not substituted or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or 0R6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 atoms of carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and, each of Zlc, Z2C and Z3C independently represent carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 atoms of carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each one of R12 and R13 which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having from 1 to 5 carbon atoms ), 5-tetrazolyl, chlorine, f loror or hydrogen. 21. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 20, wherein: ring A forms an oxo conjugated double bond together with the carbon atom attached to CH2- XC-YC; Xc is S; Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (where at least two hydrogen atoms are substituted with carboxy, C00R1 '(where R' is an alkyl or alkenyl having 1 to 4 carbon atoms ), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms) carbon), and each of Zlc, Z2C and Z3C is carboxy, C00R7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) 0 CH2OR10 '(where RIO' is hydrogen or an acyl which has 1 to 5 carbon atoms). 22. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: ring A forms a double bond conjugated to oxo together with the carbon atom which is attached to CH2-XC-YC; Yc is 2-acetylamino-2-carboxyethyl; and any of Zlc or Z2C is hydroxy and groups * ^^^ ^ ^ ^ J ^ remaining outside Zlc, Z2C and Z3C are all hydrogen. 23. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: ring A forms a conjugated oxo double bond without the carbon atom bonded to CH2 attached -XC-YC; Xc is S, O or SO; Y c is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (where at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); and each of Zlc, Z2C and Z3C is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl, having 1 to 4 carbon atoms, hydroxy or a derivative thereof, amino or a derivative group therein, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 24. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 23, wherein: ring A forms a double conjugated oxo bond without containing the carbon atom bonded to CH2- XC-YC; Xc is S, 0 or SO; Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms); carbon), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted with carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an alkyl unsubstituted or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, a substituted or unsubstituted alkyl having 1 to 4 atoms carbon or unsubstituted or substituted acyl having 1 to 5 carbon atoms); and each of Zlc, Z2C and Z3C independently represent carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, a substituted or unsubstituted alkyl having from 1 to 4 atoms S ^ fe ^ iíTS ^ T ^ TT ^ T carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represents hydrogen, a substituted or unsubstituted alkyl having from 1 to 4 carbon atoms or an unsubstituted acyl or substituted having from 1 to 5 carbon atoms), 5-tetrazolyl, chloro, fluoro and hydrogen. 25. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 24, wherein: ring A forms an oxo conjugated double bond without containing the carbon atom attached to CH2- XC-YC; Xc is S; Yc is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, C00R1 '(where R1' is an alkyl or alkenyl having 1 to 4 carbon atoms); carbon), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which may be optionally substituted with fluoro), hydroxy or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms); and, each of Zlc, Z2C and Z3C is carboxy, COOR7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) k% Éás ££ S £ yeséaá »Jtí? &? n n? 0 CH2OR10 '(where RIO' is hydrogen or an acyl which has 1 to 5 carbon atoms). 26. A cyclopentanone derivative of formula [ÍC] or a pharmacologically acceptable salt thereof, as described in claim 25, wherein: ring A forms an oxo conjugated bond without containing the carbon atom attached to CH2-XC -YC; Yc is 2-acetylamino-2-carboxyethyl; and all of Zlc, Z2C and z3c are hydrogen. 27. A ketone derivative of formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: AD is an unsubstituted or substituted aliphatic hydrocarbon group having from 1 to 4 carbon atoms; BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a derivative thereof or hydroxy or a derivative thereof); and ZD is carboxy or a group derived therefrom, a substituted alkyl or alkenyl having from 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen. 28. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 27, wherein: AD is an aliphatic hydrocarbon group having from 1 to 4 carbon atoms; BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms) carbon), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted by carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5 which may be the same or different and independently represent hydrogen, an alkyl not substituted or substituted having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having from 1 to 4 atoms carbon or an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and ZD is carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9 which may be the same or different and independently represents hydrogen 0 an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, or an unsubstituted acyl or substituted that has of 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 atoms 15 carbon), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted acyl or substituted that has 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen. 29. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 28, wherein: AD is an alkyl having 1 to 4 carbon atoms. 25 carbon; Yes 8 £ S & amp; amp; * BD is hydrogen or an alkyl having 1 to 4 carbon atoms; XD is S; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1 '(where R1' is an alkyl or alkenyl having 1 to 4 atoms carbon), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which may be hydrogen optionally substituted with fluorine); hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 atoms carbon); ZD is carboxy, C00R7 '(wherein R7' is alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO' is a hydrogen or an acyl having 1 to 5 carbon atoms) 30. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 29, wherein: AD is methyl, BD is hydrogen, X X is S, Y D is 2; -acetylamino-2-carboxyethyl or 2-acetylamino-2-methoxycarbonylethyl, and ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl 31. A ketone derivative of the formula [ID] or a salt F. pharmacologically acceptable thereof, as described in claim 1, wherein: AD is an unsubstituted or substituted aromatic hydrocarbon, an aromatic heterocyclic ring or a saturated heterocyclic ring; BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, 0, or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a derivative thereof or amino or a derivative thereof or hydroxy or a derivative thereof); and ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring , a halogen or hydrogen. 32. A ketone derivative of formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 31, wherein: AD is an unsubstituted benzene ring in which, when substituted, from 1 to 3 hydrogen atoms are substituted with an unsubstituted or substituted alkyl group having from 1 to 4 carbon atoms, a halogen, hydroxy, a jjjHg | 2 £? alkoxy having 1 to 4 carbon atoms, amino, an alkyl or dialkylamino having 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having from 1 to 5 carbon atoms, an acylamino having from 1 to 5 carbon atoms, cyano or trifluoromethyl; BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms; XD is S, O, or SO; YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms) carbon), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl which has from 1 to 4 carbon atoms 0 an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and ZD is carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein Rll is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each R12 and R13, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms carbon), 5-tetrazolyl, chlorine, fluorine or hydrogen. 33. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 32, wherein: AD is an unsubstituted or substituted benzene ring in which, when substituted, at 3 hydrogen atoms are substituted with methyl, methoxy, methoxycarbonyl, nitro, Cyan, a halogen or trifluoromethyl; BD is hydrogen or an alkyl having 1 to 4 carbon atoms; j s; YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, C00R1 '(wherein R1' is alkyl or alkenyl having 1 to 4 carbon atoms) ), NHC0R14 (wherein each R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having from 1 to 4 carbon atoms); ZD is carboxy, C00R7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms), or CH2OR10 '(wherein each of RIO' is hydrogen or an acyl having 1 (C5-C5) 34. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 33, wherein: AD is an unsubstituted benzene ring or a ring of benzene substituted with methyl or methoxy; BD is a hydrogen;? JJ TS YD 2-acetylamino-2-carboxyethyl, 2-acet ilamino-2-methoxycarbonylethyl or 2-acetylaminoethyl; and, ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl. 35. A ketone derivative of the formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: AD and BD combine together to form a cyclobutan-1-one ring having from 3 to 7 carbon atoms (except for 5 carbon atoms); XD is S, O, or SO; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a derivative thereof or hydroxy or a derivative thereof); and ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring , a halogen or hydrogen. 36. A ketone derivative of formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 35, wherein: AD and BD combine together to form a ring cyclobutan-1-one or cyclohexan-1 -one substituted or unsubstituted; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl or alkenyl having from 1 to 4 carbon atoms) carbon), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or amino or a group derived therefrom), NR4R5 (wherein each R4 and R5 which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 a 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) and ZD is carboxy, C00R7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein RIO is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, 0C0R11 (wherein Rll is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represent hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen. 37. A ketone derivative of formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 36, wherein: AD and BD combine together to form a cyclobutan-1-one ring or a cyclohexan ring -1-one; YD is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, C00R1 '(where R1' is an alkyl or alkenyl having 1 to 4 carbon atoms ), NHC0R14 (wherein R14 is an alkyl having 1 to 4 carbon atoms in which hydrogen can be optionally substituted with fluorine), hydroxy or 0C0R15 (wherein R15 is an alkyl having 1 to 4 carbon atoms) carbon); ZD is carboxy, COOR7 '(wherein R7' is an alkyl having 1 to 4 carbon atoms) or CH2OR10 '(wherein RIO' is hydrogen or an acyl having 1 to 5 carbon atoms) 38. A ketone derivative of formula [ID] or a pharmacologically acceptable salt thereof, as described in claim 37, wherein: (I) AD and BD combine together to form a cyclobutan-1-one ring , XD is S, YD is 2-acetylamino-2-carboxyethyl and ZD is carboxy; (II) AD and BD combine together to form a C-ring. iclobutan-1-one, XD is S, YD is 2-acetylamino-2-methoxycarbonylethyl and ZD is methoxycarbonyl; (III) AD and BD combine together to form a cyclobutan-1-one ring, XD is S, YD is 2,3-dihydroxy-n-propyl and ZD is acetoxymethyl; and (IV) AD and BD combine together to form a cyclohexane-1-one ring, XD is S, YD is 2-acetylamino-2-carboxyethyl, and ZD is carboxy. 39. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 1, characterized in that: AF is a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 4 carbon atoms. carbon; BF is a hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XF and YF is a straight or branched chain aliphatic hydrocarbon group having from 1 to 10 carbon atoms (wherein at least one hydrogen may be optionally substituted with carboxy or a derivative thereof, amino or a group derived therefrom , hydroxy or a group derived therefrom) or; XF and YF are each linked directly or via a hetero atom to form a monocyclic heterocyclic ring (wherein at least one hydrogen atom can be optionally substituted with an alkyl having from 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 40. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 39, wherein: AF is methyl, ethyl, n-propyl or isopropyl, which may be replaced or replaced; BF is hydrogen; each of XF and YF, which may be the same or different and independently represent an alkyl that has 1 to 6 carbon atoms or XF and YF est. { they are linked together directly or via a hetero atom to form a monocyclic heterocyclic ring which can be unsubstituted or substituted with an alkyl having 1 to 4 atoms or phenyl; ZF is carboxy, C00R1 (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having from 1 to 5 carbon atoms), hydroxy, OR 5 (wherein R 5 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or an unsubstituted or substituted acyl having from 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms ), 5-tetrazolyl, chlorine or fluorine. 41. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 40, wherein: AF is methyl; BF is hydrogen; XF and YF are both n-propyl, ethyl or isopropyl, XF and YF are each bound directly or via a hetero atom to form pyrrolidine, piperidine, morpholine, a 4-methylpiperazine ring or 4-phenylpiperazine; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms) or cyano. 42. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: AF is an unsubstituted or substituted aryl, heteroaryl or a saturated heterocyclyl ring; BF is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; XF and YF are a linear or branched aliphatic hydrocarbon group having from 1 to 10 carbon atoms (wherein at least one hydrogen may be optionally substituted with Carboxy or a derivative thereof, amino or a derivative thereof or hydroxy or a derivative thereof), or XF and YF are bonded together directly or via a hetero atom to form a heterocyclic ring (wherein at least a hydrogen can be optionally substituted with alkyl that 25 has from 1 to 4 carbon atoms, phenyl, carboxy or a group derivative thereof, amino or a group derived therefrom, or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 43. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 42, wherein: AF is a benzene ring or an unsubstituted or substituted monocyclic aromatic heterocyclic ring. BF is hydrogen; XF and YF, which may be the same or different, are a linear or branched aliphatic hydrocarbon group having from 1 to 6 or XF and YF are linked together directly or via a heteroatom to form a heterocyclic ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, COOR1 (wherein R1 is an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms or phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having from 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted acyl or substituted having 1 to 5 carbon atoms), hydroxy, 0R5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR6R7 (where each of R6 and R7, which may be the same 0 differently and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chloride or fluorine. 44. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 43, wherein: AF is an unsubstituted or substituted benzene ring wherein, when substituted, from 1 to 3 hydrogen atoms are substituted with an alkyl having from 1 to 4 carbon atoms, a halogen, hydroxy, an alkoxy having from 1 to 4 carbon atoms, amino, an alkyl or dialkylamino having from 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms, an acylamino having 1 to 5 carbon atoms, cyano or trifluoromethyl; BF is hydrogen; each of XF and YF, which may be the same independently and independently, represents an alkyl having 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom to form an unsubstituted monocyclic heterocyclic ring or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is a hydrogen or an alkyl having 1 to 4 carbon atoms), cyano or CH2OR4 '(wherein R4' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms) carbon). 45. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof according to claim 44, wherein: AF is an unsubstituted or substituted benzene ring, wherein, when substituted from 1 to 3 hydrogen atoms are substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, halogen or trifluoromethyl; BF is hydrogen; XF and YF are both ethyl, n-propyl or isopropyl; or XF and YF are attached to each other directly or via a heteroatom to form a pyrrolidine, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring; ZF is carboxy, C00R1"(where Rl" is methyl or ethyl), CONR2"R3" (where R2"and R3", which may be the same or different and each is hydrogen, methyl or ethyl) or cyano . 46. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 1, wherein: AF and BF combine together to form an unsubstituted cycloalkan-1-one ring or substituted having 3 to 7 carbon atoms or AF and BF combine together to form a cycloalkan-1-one ring, having 3 to 7 carbon atoms in the ring which is fused with an aromatic hydrocarbon or a aromatic heterocyclic ring. XF and YF are a straight or branched chain aliphatic hydrocarbon group having from 1 to 10 carbon atoms (wherein at least one hydrogen can be optionally substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom) or XF and YF are linked together directly or via a heteroatom to form a heterocyclic ring (wherein at least one hydrogen can be optionally substituted with an alkyl having 1 to 4 carbon atoms). carbon, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or hydroxy or a group derived therefrom); ZF is carboxy or a group derived therefrom, a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen 47. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 46, wherein: AF and BF combine together to form an unsubstituted cycloalkan-1-one ring or substituted having 4 to 6 carbon atoms or to form a cycloalkan-1-one ring having 4 to 6 unsubstituted or substituted carbon atoms which is fused with an aromatic hydrocarbon or a monocyclic aromatic heterocyclic ring; each of XF and YF, which may be the same or different and independently is a straight or branched chain aliphatic hydrocarbon group having from 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom for forming a monocyclic heterocyclic ring, which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, C00R1 (wherein R1 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represent hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is a hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or unsubstituted acyl or substituted having 1 to 5 carbon atoms), hydroxy, 0R5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or an unsubstituted or substituted acyl having 1 to 5 carbon atoms) carbon, preferably an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently they represent hydrogen, an alkyl having 1 to 4 carbon atoms carbon), or an acyl having 1 to 5 carbon atoms, 5-tetrazolyl, chlorine or fluorine. 48. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 47 wherein: AF and BF combine together to form an unsubstituted cyclopentan-1-one ring or substituted or to form an unsubstituted or substituted cyclopentan-1-one ring fused with benzene or a monocyclic aromatic heterocyclic ring; each of XF and YF, which may be the same 0 differently and independently are an alkyl having 1 to 6 carbon atoms or XF and YF are linked together directly or via a heteroatom to form a monocyclic heterocyclic ring, which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl; ZF is carboxy, C00R1 '(wherein R1' is an alkyl having 1 to 4 carbon atoms), C0NR2 'R3' (wherein R2 'and R3', which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms), cyano or CH2OR4 '(wherein R4' is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms ). 49. A β-disubstituted amino ketone derivative of formula [1F] or a pharmacologically acceptable salt thereof, as described in claim 48, wherein: AF and BF combine together to form a cyclopentan-1-one ring or a indan-1-one ring; XF and YF are linked together directly or via a heteroatom to form a pyrrolidone, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring; and ZF is carboxy, C00R1"(where R1" is methyl or ethyl), CONR2"R3" (wherein R2"and R3", which may be the same or different and each is hydrogen, methyl or ethyl) or cyano. 50. A pharmaceutical composition comprises as an effective ingredient a cyclopentanone derivative of formula [AA] as described in claim 1, or a cyclopentanone derivative according to any of claims 2 to 6 or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes: (1) when Z1A and Z2A they are hydrogen, XA is S, YA is methyl or benzyl and Z3A is methoxycarbonyl, 5 (2) when Z1A and Z2A is hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is 0, Z1A is hydroxy or a group derived from same, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-l-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen. 51. A composition for the treatment of diseases of the central nervous system which comprises An effective ingredient a cyclopentanone derivative of formula [IA] as described in claim 1 or a cyclopentanone derivative as described in any of claims 2 to 6, or a pharmacologically acceptable salt wherein the cyclopentanone derivative furthermore 25 includes: Ktí? I *? I? »2-ftrl _Zi Ja 1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and Z3A is methoxycarbonyl, 2) when Z1A and Z2A are hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; 5 3) XA is N or 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; 4) XA is 0, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; 0 5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a group 5 derived therefrom and Z3A is hydrogen. 52. A composition for the treatment of nervous diseases of the peripheral system, comprising a cyclopentanone derivative as an effective ingredient of formula [IA] as described in claim 1 or a cyclopentanone derivative of any of claims 2 to 6. or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes: (1) when Z1A and Z2A are hydrogen, XA is S, YA is 5 methyl or benzyl, and Z3A is methoxycarbonyl, (2) when Z1A and Z2A are hydrogen, XA is 0 or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or 0, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) XA is 0, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is 0, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a derivative thereof and Z3A is hydrogen; 53. A composition for promoting nerve cell differentiation, comprising as an effective ingredient a cyclopentanone derivative of formula [IA] as described in claim 1, or a cyclopentanone derivative as described in any of claims 2 to 6. or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes: (1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl, and Z3A is methoxycarbonyl, (2) when Z1A and Z2A are hydrogen , XA is O or N, YA is benzyl and Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl; (3) XA is N or O, Z1A and Z3A are hydrogen and Z2A is carboxy or methoxycarbonyl; (4) Xs is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and Z3A is amino or a group derived therefrom; 5 (5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and Z2A and Z3A are hydrogen; (6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and Z2A and Z3A are hydrogen; (7) Z1A is S, SO or S02, Z2A is hydroxy or a group 10 derived therefrom and Z3A is hydrogen. 54. A pharmacological composition comprising as an effective ingredient a 2,3-disubstituted cyclopentanone derivative of the formula [IB] or a 2,3-disubstituted cyclopentanone derivative as described in any of claims 7 to 18, or a pharmacologically acceptable salt thereof. 55. A composition for the treatment of diseases of the central nervous system comprising a 2,3-disubstituted cyclopentanone derivative as an ingredient 20 of formula [IB] or a 2,3-disubstituted cyclopentanone derivative as described in any of claims 7 to 18 or a pharmacologically acceptable salt thereof. 56. A composition for the treatment of 25 diseases of the peripheral nervous system which comprises z & £? ^., ^ i »z. - Sftifeirifea & l-1-f - effective ingredient a 2,3-disubstituted cyclopentanone derivative of the formula [IB] or a 2,3-disubstituted cyclopentanone derivative as described in any of claims 7 to 18 or a pharmacologically acceptable salt thereof. 57. A composition for promoting nerve cell differentiation comprising as an effective ingredient a 2,3-disubstituted cyclopentanone derivative of formula [IB] or a 2,3-disubstituted cyclopropane derivative as described in any one of claims 7 to 18 or a pharmacologically acceptable salt thereof. 58. A pharmacological composition comprising as an effective ingredient a cyclopentanone derivative of formula [ÍC] or a cyclopentanone derivative as described in any of claims 19 to 26 or a pharmacologically acceptable salt thereof, wherein the derivative of Cyclopentanone further includes the cases that when Xc is 0 or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 59. A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a cyclopentanone derivative of formula [ÍC] or a cyclopentanone derivative as described in any of claims 19 to 26, or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 60. A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a cyclopentanone derivative of the formula [C] or a cyclopentanone derivative as described in any of claims 19 to 26, or a pharmacologically acceptable salt thereof. , wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen or a hydroxy, or a group derived therefrom. 61. A composition for promoting nerve cell differentiation comprising as an effective ingredient a cyclopentanone derivative of formula [C] or a cyclopentanone derivative as described in any of items 19 to 26, or a pharmacologically acceptable salt thereof, in wherein the cyclopentanone derivative further includes the cases that when Xc is O or NH, Zlc and Z3C are hydrogen and Z2C is hydrogen or hydroxy or a group derived therefrom. 62. A pharmacological composition comprising as an effective ingredient a ketone derivative of formula [ID] according to claim 1, or a ketone derivative as described in any of claims 26 to 38, or a pharmacologically acceptable salt thereof. , wherein AD and BD combine together to form a cyclobutane ring, the ketone derivative further includes from (1) to (4): (1) XD is O, YD is methyl, n-octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is 0, YD is benzyl and ZD is benzyloxymethyl; (3) XD is 0, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is a substituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 63. A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a ketone derivative of the formula [ID] as described in claim 1, or a ketone derivative according to any of claims 26 to 38 , or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes subparagraphs (1) to (4): (1) XD is 0, YD is methyl, n-octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is 0, YD is benzyl and ZD is benzyloxymethyl; (3) XD is O, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 64. A composition for the treatment of peripheral nervous system diseases comprising as an effective ingredient a ketone derivative of formula [ID] according to claim 1, or a ketone derivative as described in any of claims 26 to 38 , or a pharmacologically acceptable salt thereof, wherein when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes subparagraphs (1) to (4): (1) XD is O, YD is methyl , n-octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is O, YD is benzyl and ZD is benzyloxymethyl; (3) XD is O, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 65. A composition for promoting nerve cell differentiation comprising as an effective ingredient a ketone derivative of formula [ID] as described in claim 1, or a ketone derivative as described in any of claims 26 to 38, or a pharmacologically acceptable salt thereof, wherein AD and BD combine together to form a cyclobutane ring, the ketone derivative further includes subparagraphs (1) to (4): (1) XD is 0, YD is methyl, n- octyl or n-hexadecyl and ZD is methoxycarbonyl; (2) XD is 0, YD is benzyl and ZD is benzyloxymethyl; (3) XD is 0, YD is p-methoxybenzyl and ZD is p-methoxybenzyloxymethyl; and (4) XD is 0, YD is trifly and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy. 66. A pharmacological composition comprising as an effective ingredient a compound of formula [ÍE], or a pharmacologically acceptable salt thereof. 67. A composition for the treatment of diseases of the central nervous system which comprises as an effective ingredient a compound of formula [ÍE], or a pharmacologically acceptable salt thereof. 68. A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a compound of formula [ÍE], or a pharmacologically acceptable salt thereof. 69. A composition for promoting nerve cell differentiation comprising as an effective ingredient a compound of formula [ÍE], or a pharmacologically acceptable salt thereof. 70. A pharmacological composition comprising as an effective ingredient a β-disubstituted amino ketone derivative of the formula [1F], or a β-disubstituted amino ketone derivative as described in any of claims 39 to 49 described above, or a pharmacologically acceptable salt of the same, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further includes those wherein BF is hydrogen, XF is directly linked to YF to form a piperidine ring and ZF is carboxy. 71. A composition for the treatment of diseases of the central nervous system comprising as an effective ingredient a β-disubstituted amino ketone derivative of the formula [1F], or a β-disubstituted amino ketone derivative as described in any of claims 39 to 49 , or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further includes those in which BF is hydrogen, XF is directly attached to YF to form a peripheral ring and ZF It is carboxy. 72. A composition for the treatment of diseases of the peripheral nervous system which comprises as an effective ingredient a ß-disubstituted amino ketone derivative of formula [1F], or a β-disubstituted amino ketone derivative as described in any of claims 39 to 49 described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further includes those in which BF is hydrogen, XF is directly linked to YF to form a piperidine ring and ZF is carboxy. 73. A composition for promoting nerve cell differentiation comprising as an effective ingredient a β-disubstituted amino ketone derivative of formula [1F], or a β-disubstituted amino ketone derivative as described in any of claims 39 to 49 described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the β-disubstituted amino ketone derivative further include those wherein BF is hydrogen, XF is directly attached to YF to form a piperidine ring and ZF is carboxy .