JPH06192199A - Ketone derivative - Google Patents

Abstract

PURPOSE:To obtain the novel ketone derivative consisting of a 3-(2-protected aminio-4-methylvalerylamino)-1-furfurylthio-2-heptanone, having a thioprotease- inhibitory activity, and useful for treating muscular dystrophy, etc. CONSTITUTION:A chloromethyl ketone derivative of formula I [Boc is butoxycarbonyl; R<6> is H, 1-5C alkyl; R<7> is (substituted)1-5C alkoxy, 6-14C aryloxy, etc.; R<8> is H, 1-5C alkyl, etc.,] is reacted with a mercaptan of the formula: R<9>SH [R<9> is (substituted)6-14C aryl, etc.,] in the presence of a base, and the protecting group is removed from the protected amino group of the reactional product. The produced amine of formula II is reacted with an amino acid derivative of formula III [R<4> is the same as R<6>; R<5> is H, (substituted)6-14C aryl, (substituted)1-20C alkyl etc.; R<12> is R<10>CO (R<10> is 3-15C cycloalkyl, etc.), R<10>OCO, etc.] and, if necessary, further oxidized to obtain the objective ketone derivative of formula IV (R<1> is R<12>, etc.; R<2> is the same as R<6>; R<3> is the same as R<6> A is S, SO, SO2).

Description

Detailed Description of the Invention [0001] The present invention relates to a novel ketone derivative.
In detail, papain, cathepsin B, cathepsin H,
For thiol proteases such as cathepsin L and calpain
New ketone derivatives with strong inhibitory effect on
It [0002] PRIOR ART AND PROBLEMS TO BE SOLVED BY THE INVENTION Daddy
In, cathepsin B, cathepsin H, cathepsin L, mosquito
In vivo function of thiol protease such as lupain
As it is elucidated, the abnormal increase in the cause of various diseases
It has been found that there is also a thiol protea
Ze inhibitors were effective in animal models of those diseases
The number of reports is increasing. Muscle diseases such as muscular dystrophy and muscular atrophy
In skeletal muscle collapse seen in
Thiol proteases such as protein B are components of muscle fiber proteins.
That they are involved in the initial process such as the disappearance of Z-rays through the solution
Considered (Metabolism, 25, 183 pages, 198)
8 years). In addition, E- which is a thiol protease inhibitor
64-d extended in muscular dystrophy hamsters
It has been reported that there were effects such as life effects (Journ
al of Pharmacobio Dynamic
s, vol. 10, page 678, 1987). Therefore,
All protease inhibitors are muscular dystrophy, muscle atrophy
It is thought that it can be used as a therapeutic drug for diseases. Odors of ischemic diseases such as myocardial infarction and stroke
The main cause of cell damage after ischemia is xanthine oxidation.
It is active oxygen produced by oxygen. C increased in the process of ischemia
a²⁺Calpain activated by concentration is xanthine
A limited amount of xanthine dehydrogenase, a precursor of oxidase
There is a theory that it is converted to oxidase (New)
England Journal of Medici
ne, 312, 159, 1985). Also,
Calpain activation is directly linked to cardiomyocyte necrosis and cerebral nerve cell death.
It is thought that it can also be a direct cause (modern medicine,
43, page 783, 1988). Calpain inhibition
Drug NCO-700 is effective in animal model of myocardial infarction
It has been reported that there is (Arzneimitte
l Forschung / Drug Research
h, 36, 190 pages, 671 pages, 1986
, And E-64-C is a microtubule-binding protein after cerebral ischemia.
Suppresses decomposition (Brain Research,
526, p. 177, 1990). Therefore, Cal
Pine inhibitors are ischemic diseases such as myocardial infarction and stroke
It is thought to be a remedy for. Elderly people unique to Alzheimer's disease brain
A protein called amyloid is deposited on the plaque.
Amyloid is involved in the degradation of amyloid protein precursor (APP)
Is known to produce more. With normal metabolism of APP
Does not produce amyloid, but has an abnormally elevated protea
The abdominal metabolism of azide produces amyloid, which
It is thought that it will become a human spot (Scientific
American, November 1991 issue, page 40
J). Therefore, inhibitors of proteases are
-It is expected to be a cure for disease. In a rabbit head injury model, a carpa
Has been reported to be activated (Neu
rochical Research, 16 volumes, 48
3 pages, 1991), also a model of rat head injury
Treatment with leupeptin, a calpain inhibitor
, A protective effect on axons has been observed (J
individual of Neurosurgery, 65
Vol. 92, p. 1986). Therefore, calpine blockade
Harmful drugs improve consciousness disorder and movement disorder in head injury
It is thought that there is an effect such as. Myelin binding in dendrites of nerve cells
There is a report that synthetic protein is degraded by calpain
(Journal of Neurochemistr
y, 47, 1007, 1986). Therefore,
Calpain inhibitors are caused by neuronal demyelination.
Diseases such as multiple sclerosis and peripheral nerve neuropa
It is thought to be effective against sea. Many of the cataracts are found in the lens.
Crystallin, a water-soluble protein, acts as a protease
It is said that the lens becomes cloudy due to more hydrolysis.
Has been. Experimental model of cataracts and certain human cataracts
In the disorder, the calcium concentration in the lens is increased (I
nvestigative Ophthalmolog
y & Visual Science, 28, 17
02 pages, 1987, Experimental
Eye Research, 34, 413 pages, 1
982), and the protease contained in the lens
Calpain is the most common (Lens
and Eye Toxicity Research
h, Vol. 6, 725, 1989), Calpine
Hyperactivity is believed to be one of the causes of cataracts
It Calpain inhibitor E-64 is a cataract experiment
Reported that the model was effective (Investigat
iveOphthalmology & Visual
  Science, 32, 533 pages, 1991.
, So calpain inhibitors are a treatment for cataracts.
It is thought to be a medicine. [0009] Neutrophils, which are deeply associated with inflammation, are chemotactic
Degranulation and stimulation by factors and phorbol ester
Known to respond to the production of superoxide
This is mediated by protein kinase C (PKC).
Is believed to have been mediated. Calpine is this PK
It has a function of activating C and promotes degranulation.
Is said to have a suppressive effect on superoxide production
There is a report (Journal of Biological
al Chemistry, Volume 263, Page 1915
J., 1988). In addition, in rat macrophages
The concentration of cathepsin B in the blood
Is also 30 to 40 times higher, and the enzyme of inflammatory macrophages
Reported to be 6 times higher than normal macrophages
It is (Journal of Biochmist
ry, 98, 87 pages, 1985). These things
Therefore, thiol protease inhibitors are anti-inflammatory agents.
It is thought that it can be used. A type I allergic reaction is a sensitization of an organism to an antigen.
Immunoglobulin E (IgE) produced by
Proceed through. Is a thiol protease inhibitor
Estatin A specifically suppresses IgE production and
It is reported that it does not affect the production of G (The
  Journal of Antibiotics, 4
Volume 2, page 1362, 1989). Therefore, Thio
Leprotease inhibitors used as antiallergic agents
It is considered possible. When hepatocytes are necrotic, the cell membrane is damaged.
By Ca²⁺The intracellular permeability of Ca²⁺High concentration
Therefore, calpain is a substrate of calpain
Is thought to cause cell death due to degradation of skeletal proteins
There is. Therefore, calpain inhibitors are a treatment for fulminant hepatitis.
Can be used. Cathepsin B, Cathepsin L, etc.
Cathepsins degrade bone collagen within osteoclasts
Are involved in. Bone destruction by administering parathyroid hormone
E-, which is an inhibitor of cathepsins, in the enhanced rat
64 or Estatin A gives blood calci
The concentration of um and hydroxyproline may decrease.
Reported (Biochemical and B
iophysical Research Commu
animation, vol. 125, page 441, 1984
Year; JP-A-2-218610). Therefore, the cathep
Synthetic inhibitors are used to treat osteoporosis, hypercalcemia, etc.
It is considered to be a medical treatment. As a substrate for calpain, estrogen receptor
And sex hormone receptors such as the androgen receptor
And calpain can activate these receptors.
Are known. Therefore, the hyperactivity of calpain is
Diseases thought to be due to abnormal activation of mon receptors, eg
It is said to cause breast cancer, prostate cancer, and prostate enlargement
And calpain inhibitors are therapeutic agents for the above diseases
it is conceivable that. As cells become cancerous, epidermal growth factor (EG
F) It is said that the receptor is activated, and calpain
It is known that it activates EGF receptor as a substrate.
Has been. In addition, adult T-cell human leukemia virus (A
In cells infected with TLV / HTLV-1)
There is a report that pine was activated (Biochemistry, 5
7, 1202 pages, 1985). Meanwhile, cathepsies
B promotes collagen degradation, an important step in cancer translocation
Progressing, or directly degrading collagen,
Because of the close relationship with the plasma membrane of neoplastic cells,
It is said to be greatly involved in the dislocation process (T
umor Progression and Mark
ers, p. 47, 1982, Journal o
f Biological Chemistry, 25
6, 8536, 1984). These things
Et al., Thiol protease inhibitors,
It is thought to be effective for position prevention. When platelets are activated, they cause aggregation and
Cause plug. E-64- which is an inhibitor of calpain
d suppressed thrombin-induced platelet aggregation
There is a report of (Thrombosis Research
h, 57, 847, 1990). According to
Therefore, calpain inhibitors are used as platelet aggregation inhibitors.
Can be As described above, thiol protea
Abnormal hypertension causes various diseases and
Some thiol protease inhibitors are available in animal models.
It is reported to be effective. However, known inhibitors
Is E-64 (Agricultural and B
iological Chemistry, Volume 42, 5
29, 1978), E-64-d (Journ.
al of Biochemistry, Volume 93, 13
05 page, 1983), NCO-700 (JP-A-5
No. 8-126879), estatin A, B (The
  Journalof Antibiotics, 42
Vol., P. 1362, 1989), etc.
Acid derivative or peptide chloromethyl ketone (Jo
internal of Biochemistry, 99
Vol., P. 173, 1986) and acyloxymethyl
Ketone (Biochemistry, Volume 30, 4678)
Page, 1991) α-substitution of peptides represented by
Most are irreversible inhibitors such as ketones. Generally
Reversible inhibitors are non-specific with biological components other than the target enzyme
It is said that it is highly toxic because it easily reacts with
Few compounds have been used in the bed. Also, as a reversible inhibitor
Leupeptin (The Journalof An
tibiotics, Volume 22, 183 pages, 1969
Year), Calpeptin (Journal of Enzy)
me Inhibition, Volume 3, 195 pages, 1
990) and other peptidyl aldehydes are known
However, chemical stability, in vivo stability, cell membrane permeability
It is said that there is a problem with. [0016] Therefore, the present inventors have
Thio has excellent oral absorption, tissue translocation, and cell membrane permeability
The results of research on reversible inhibitors of proteases
As a result, the present invention has been completed. That is, the gist of the present invention
The effect is represented by the following general formula (I) [0017] [Chemical 8](R^TenIs C₃~ C₁₅A cycloalkyl group of
C₃~ C₁₅Having a cycloalkenyl group, a substituent of
Good C₆~ C₁₄Even if it has an aryl group or a substituent
Good C_Ten~ C₁₄Partly hydrogenated aryl groups, full
Olenyl group, optionally substituted heterocyclic residue, C
₃~ C₁₅Having a cycloalkyloxy group, a substituent of
May be C₆~ C₁₄Having an aryloxy group, a substituent of
May be C₆~ C₁₄Partly hydrogenated aryl
An oxy group, a heterocyclic oxy group which may have a substituent,
C which may have a substituent₇~ C₂₀The Aralkyl Oki
Si group and C which may have a substituent₆~ C₁₄The ant
Even if it has one or more substituents selected from the group
Good C₁~ C₂₀Alkyl group of C₃~ C₁₅The cycloal
Kill group; C which may have a substituent₆~ C₁₄Ally
Group; C which may have a substituent₆~ C₁₄Part of hydrogen
Aryl group added; C which may have a substituent₂
~ C_TenMay have an alkenyl group or a substituent
Represents a heterocyclic residue. ), R², R^FourAnd R⁶Is
Independently hydrogen atom or C₁~ C_FiveThe alkyl
Represents a group, R³And R^FiveAre independent hydrogen
Child, C₇~ C₂₀Having aralkyloxy groups and substituents
May be C₆~ C₁₄Aryl group of C₁~ C_TenThe al
C optionally having a cooxy group or a substituent₁~ C₂₀of
Represents an alkyl group. Also R²And R³, R^FourAnd R^FiveIs it
Nitrogen-containing heterocycles, each of which may together have a substituent
You may form a ring. R⁷Is C₃~ C₁₅Cycloarch
Group, hydroxyl group, or heterocyclic residue
Good C₁~ C_FiveAlkoxy group of C₆~ C₁₄Aryl
Oxy group, C₇~ C₂₀Aralkyloxy group, heterocyclic residue
C optionally substituted with a group₁~ C_FiveAlkylthio
Base, C₆~ C₁₄Arylthio group of C₇~ C₂₀Aral
Kirthio group, carboxyl group, carbamoyl group, C₂~
C₆Alkoxycarbonyl groups, heterocyclic residues and substitutions of
C which may have a group₆~ C₁₄Selected from aryl groups
C optionally having one or more substituents₁~ C₂₀A
Rualkyl group; hydrogen atom; C₇~ C₂₀Aralkyloxy
Group; C which may have a substituent₆~ C₁₄Aryl group
Or C₁~ C_TenRepresents an alkoxy group of R⁸Is hydrogen
Child, C₁~ C_FiveHaving an alkyl group or a substituent of
Good C₇~ C₂₀Represents an aralkyl group of R⁷And R⁸
Together with benzylidene optionally having a substituent
Group or C₃~ C₁₅Represents a cycloalkyl group. [0019] [Chemical 9] R⁹Is C which may have a substituent₆~ C
₁₄Aryl group or-(CH₂) m -X (X is hydrogen source
Child, hydroxyl group, C₁~ C_FiveAlkylthio group of C
₂~ C₆Alkoxycarbonylamino group of
Optionally substituted heterocyclic residue, amino group, C₁~ C_FiveMo
Noalkylamino group, C₂~ C_TenDialkylamino
Base, C₂~ C₆Acylamino group, halogen atom, C₁
~ C_FiveAlkoxy group, optionally substituted C₆
~ C₁₄An optionally substituted aryl group or C
₆~ C₁₄Represents an aryloxy group, and m is 0 or 1
Represents an integer of 15. ) Represents. However, R¹Is benzylo
Represents a oxycarbonyl group, R^Four, R⁶And R⁸Together
Represents a hydrogen atom, R^FiveRepresents a benzyl group, R⁷Is meth
Represents a radical group and n represents 0, -AR⁹Is meth
Does not represent a ruthio group. (2) When A represents -O-, R⁹Is water
Elementary atom or-(CH₂)_l-X (l is an integer from 1 to 15
Where X is as defined above. ) Represents. [0022] [Chemical 10]C₂₀Represents an alkyl group. ) Represents R⁹Is a substituent
May have C₆~ C₁₄Aryl group of or
(CH₂) m-X (X and m are as defined above.
It ) Represents. Also R⁹And R¹¹Together, the substituents
It may form a nitrogen-containing heterocycle which may have. Further, n represents 0 or 1. ]]
Ketone derivative or a pharmaceutically acceptable salt thereof, and
It exists in a pharmaceutical composition containing this as an active ingredient. Hereafter,
The details will be explained in detail. R in the general formula (I)^Ten
C defined by₁~ C₂₀The alkyl group of is methyl
Group, ethyl group, propyl group, isopropyl group, butyl
Group, isobutyl group, sec-butyl group, tert-butyl group
Group, pentyl group, isopentyl group, neopentyl group,
tert-pentyl group, hexyl group, isohexyl group,
Heptyl group, octyl group, nonyl group, decyl group, unde
Syl group, dodecyl group, tridecyl group, tetradecyl group,
Pentadecyl group, hexadecyl group, heptadecyl group, o
Cutadecyl group, nonadecyl group, icosyl group, etc.
The alkyl group is a cyclopropyl group or a cyclobutyl group.
Group, cyclopentyl group, cyclohexyl group, cyclohexyl group
Butyl, cyclooctyl, cyclononyl, cyclo
Decyl group, cycloundecyl group, cyclododecyl group,
Clotridecyl group, cyclotetradecyl group, cyclopen
C such as tadecyl group₃~ C₁₅Cycloalkyl group of; cyclo
Propenyl group, cyclobutenyl group, cyclopentenyl group
Group, cyclohexenyl group, 1,4-cyclohexadienyl group
Group, cycloheptenyl group, cyclooctenyl group, cyclo
Rodecenyl group, cyclododecenyl group, cyclopentadecene
C such as nyl group₃~ C₁₅Cycloalkenyl group of phenyl
Group, 1-naphthyl group, 2-naphthyl group, anthryl group, etc.
C₆~ C₁₄Aryl group of 1,2-dihydronaphthyl
Group, C such as 1,2,3,4-tetrahydronaphthyl group_Ten
~ C₁₄Partially hydrogenated aryl groups; fluorenyl
Group; furan ring, dihydrofuran ring, tetrahydrofuran
Ring, pyran ring, dihydropyran ring, tetrahydropyran
Ring, benzofuran ring, dihydrobenzofuran ring, isobe
Nzofuran ring, chromene ring, chroman ring, isochroman
Ring, thiophene ring, benzothiophene ring, pyrrole ring,
Pyrroline ring, pyrrolidine ring, imidazole ring, imidazo
Phosphorus ring, imidazolidine ring, pyrazole ring, pyrazoline
Ring, pyrazolidine ring, triazole ring, tetrazole
Ring, pyridine ring, pyridine oxide ring, piperidine ring,
Pyrazine ring, piperazine ring, pyrimidine ring, pyridazine
Ring, indolizine ring, indole ring, indoline ring, a
Soindole ring, isoindoline ring, indazole ring,
Benzimidazole ring, purine ring, quinolidine ring, quino
Phosphorus ring, phthalazine ring, naphthyridine ring, quinoxaline
Ring, quinazoline ring, cinnoline ring, pteridine ring, oki
Sazole ring, oxazolidine ring, isooxozar ring,
Isoxazolidine ring, thiazole ring, thiazolidine ring,
Isothiazole ring, isothiazolidine ring, dioxolane
Ring, dioxane ring, dithiane ring, morpholine ring, thiomo
Select from oxygen atom, sulfur atom, nitrogen atom such as ruphorin ring
Has 1 to 4 heteroatoms, and the total number of atoms constituting the ring
Is a heterocyclic residue of 5 to 10; cyclopropyloxy group,
Crobutyloxy group, cyclopentyloxy group, cyclo
Hexyloxy group, cycloheptyloxy group, cyclo
Cutyloxy group, cyclodecyloxy group, cyclododecyl
C such as luoxy group and cyclopentadecyloxy group₃~ C
₁₅Cycloalkyloxy group; phenoxy group, 1-naphtho
C such as tyloxy group and 2-naphthyloxy group₆~ C₁₄of
Aryloxy group; 1,2,3,4-tetrahydro-1
-Naphthyloxy group, 1,2,3,4-tetrahydro-
2-naphthyloxy group, 5,6,7,8-tetrahydro
-1-naphthyloxy group, 5,6,7,8-tetrahydr
C such as 2--2-naphthyloxy group₆~ C₁₄Part of hydrogenation
Added aryloxy group; 2-tetrahydrofuryl
Xy group, 3-tetrahydrofuryloxy group, 2-tetra
Hydropyranyloxy group, 3-tetrahydropyranylo
Xy, 3-pyrrolyloxy, 1-piperazinyloxy
Si group, 3-morpholinyloxy group, 4-morpholinyloxy group
Xy, 2-pyridyloxy, 3-pyridyloxy
Group, 4-pyridyloxy group, etc. oxygen atom, sulfur atom, nitrogen atom
It has 1 to 4 heteroatoms selected from elementary atoms and forms a ring.
A heterocyclic oxy group having 5 to 10 total atoms; benzyl
Oxy group, 1-phenylethoxy group, 2-phenyleth
Xyl group, 1-phenylpropoxy group, 2-phenylpropoxy group
Poxy group, 3-phenylpropoxy group, 4-phenyl group
Toxy group, 5-phenylpentyloxy group, 1-naphthyl
Rumethoxy group, 2-naphthylmethoxy group, 1- (1-na
(Futyl) ethoxy group, 2- (1-naphthyl) ethoxy
Group, 1- (2-naphthyl) ethoxy group, 2- (2-naphtho)
Cyl) ethoxy group, etc.₇~ C₂₀Aralkyloxy
Group; and phenylthio group, 1-naphthylthio group, 2-
C such as naphthylthio group₆~ C₁₄Selected from the arylthio groups of
It may have one or more substituents that can be identified. Also R^Tenso
C defined₃~ C₁₅Cycloalkyl group, C₆~ C₁₄
Aryl group of C₆~ C₁₄A partially hydrogenated ally
Examples of the substituents and heterocyclic residues include the above-mentioned substituents.
And C₂~ C_TenThe alkenyl group of is a vinyl group, 1-
Propenyl group, allyl group, isopropenyl group, 1-butene
Nyl group, 2-butenyl group, 1-pentenyl group, 1-hexyl group
Cenyl group, 1-heptenyl group, 1-octenyl group, 1-
Examples thereof include nonenyl group and 1-decenyl group. Such a
The alkenyl group is the above-mentioned C₃~ C₁₅A cycloalkyl group of
C which may have a substituent₆~ C₁₄The aryl group of
A heterocyclic residue which may have a substituent, C₃~ C₁₅Shiku
Low alkyloxy group, optionally substituted C₆~
C₁₄An aryloxy group, which may have a substituent
Elementary ring oxy group, C which may have a substituent₇~ C₂₀of
Aralkyloxy group and C which may have a substituent
₆~ C₁₄One or more substituents selected from the arylthio groups of
May have. R², R^FourAnd R⁶Defined in
C₁~ C_FiveThe alkyl groups of are methyl group, ethyl
Group, propyl group, isopropyl group, butyl group, isobutyl
Group, sec-butyl group, tert-butyl group, pliers
Group, isopentyl group, neopentyl group, tert-pepyl group
And the like. R³And R^FiveDefined in
An optionally substituted C₁~ C₂₀The alkyl
As a group, R^TenGroups similar to those defined in
Such alkyl groups are fluorine atoms, chlorine atoms, bromine
Halogen atom such as child; R^TenC as defined in₃
~ C₁₅Cycloalkyl group; hydroxyl group; R^TenFixed by
May be substituted with the same heterocyclic residue as defined above
Methoxy, ethoxy, propoxy, isopropoxy
Si group, butoxy group, isobutoxy group, sec-butoxy group
Group, tert-butoxy group, pentyloxy group, isopene
Nyloxy group, neopentyloxy group, tert-pe
C such as an ethyloxy group₁~ C_FiveAn alkoxy group of R^Tenso
C as defined₆~ C₁₄An aryloxy group of
R^TenC as defined in₇~ C₂₀Aralkillo
Xy group; mercapto group; R^TenThe same as the one defined in
Methylthio group, which may be substituted with a ring residue, ethyl
Thio group, propylthio group, isopropylthio group, butyl
Thio group, isobutylthio group, tert-butylthio group,
C such as pentylthio group and isopentylthio group₁~ C_Fiveof
Alkylthio group; R^TenC as defined in₆~ C
₁₄Arylthio group; benzylthio group, 1-phenylene
Cylthio group, 2-phenylethylthio group, 1-naphthyl
C such as methylthio group and 2-naphthylmethylthio group₇~ C
₂₀Aralkylthio group; carboxyl group; carbamoyl
Group; methoxycarbonyl group, ethoxycarbonyl group,
Ropoxycarbonyl group, isopropoxycarbonyl group,
Butoxycarbonyl group, isobutoxycarbonyl group, t
ert-butoxycarbonyl group, pentyloxycarbo
C such as nyl group and isopentyloxycarbonyl group₂~ C
₆An alkoxycarbonyl group of R^TenSame as defined in
-Like heterocyclic residue; amino group; methylamino group, ethyl group
Mino group, propylamino group, isopropylamino group, etc.
C₁~ C_FiveMonoalkylamino group; dimethylamino
Group, ethylmethylamino group, diethylamino group, etc. C₂
~ C_TenDialkylamino group of methoxycarbonylami
Group, ethoxycarbonylamino group, propoxycarbo
Nylamino group, isopropoxycarbonylamino group,
Toxycarbonylamino group, isobutoxycarbonyl group
Mino group, tert-butoxycarbonylamino group, pen
Cyloxycarbonylamino group, isopentyloxyca
C such as rubonylamino group₂~ C₆Alkoxy Carboni
Luamino group; acetylamino group, propionylamino
Group, butyrylamino group, isobutyrylamino group, valery
C such as ruamino group and isovalerylamino group₂~ C₆A
Silamino group; guanidyl group; oxo group; and phenyl
Group, tolyl group, 1-naphthyl group, 2-naphthyl group, a
C such as anthryl group₆~ C₁₄1 selected from the aryl groups of
It may have the above substituents. C₇~ C₂₀Aral
Kiroxy group, and C₆~ C₁₄As the aryl group of
R^TenGroup similar to those defined in₁~ C_Ten
Examples of alkoxy groups include methoxy, ethoxy, and
Poxy, isopropoxy, butoxy, isobutoxy
Group, sec-butoxy group, tert-butoxy group,
Nyloxy group, isopentyloxy group, neopentyl
Oxy group, tert-pentyloxy group, hexyloxy
Si group, isohexyloxy group, heptyloxy group, octyl
Examples thereof include a tyloxy group and a decyloxy group. R²And R³, R^FourAnd R^FiveForm together
Examples of the nitrogen-containing heterocycle to be formed include a pyrrolidine ring and piperidi
Ring, 1,2,3,4-tetrahydroquinoline ring, 1,
2,3,4-tetrahydroisoquinoline ring, perhydro
Heteroatoms such as quinoline ring and perhydroisoquinoline ring
1 to 4 and the total number of atoms constituting the ring is 5 to 10
One of them is. There is a substituent on such a heterocycle
You may stay. R⁷C defined by₇~ C₂₀Aralkyl
An oxy group, and C₆~ C₁₄R is an aryl group of^Ten
Group similar to those defined in₁~ C_TenA
R as a lucoxy group³And R^FiveSame as defined in
Such groups can be mentioned. C which may have a substituent₁~
C₂₀The alkyl group of R is R^TenSame as defined in
And the alkyl group is R^TenDefined in
C similar to₃~ C₁₅Cycloalkyl group of hydroxy
R group; R^TenSubstituted with a heterocyclic residue similar to that defined in
Optionally substituted methoxy group, ethoxy group, propoxy group
Group, isopropoxy group, butoxy group, isobutoxy group,
sec-butoxy group, tert-butoxy group, pentyl
Oxy group, isopentyloxy group, neopentyloxy
Group, C such as tert-pentyloxy group₁~ C_FiveThe al
Coxy group; R^TenC as defined in₆~ C₁₄A
Reeloxy group; R^TenC as defined in₇~ C
₂₀Aralkyloxy group; R^TenSimilar to that defined in
A methylthio group which may be substituted with a heterocyclic residue, ethyl
Ruthio, propylthio, isopropylthio, buty
Ruthio group, isobutylthio group, tert-butylthio group
Group, pentylthio group, isopentylthio group, etc. C₁~ C
_FiveAlkylthio group of R;^TenC as defined in₆
~ C₁₄Arylthio group; benzylthio group, 1-phenyl
Ruethylthio group, 2-phenylethylthio group, 1-naphth
C such as tylmethylthio group and 2-naphthylmethylthio group₇
~ C₂₀Aralkylthio group; carboxyl group; carbamo
Iyl group; methoxycarbonyl group, ethoxycarbonyl group
Group, propoxycarbonyl group, isopropoxycarbonyl group
Group, butoxycarbonyl group, isobutoxycarbonyl
Group, tert-butoxycarbonyl group, pentyloxy
C such as carbonyl group and isopentyloxycarbonyl group
₂~ C₆An alkoxycarbonyl group of R^TenDefined in
A heterocyclic residue similar to that of; and a phenyl group, a tolyl group,
C such as 1-naphthyl group, 2-naphthyl group and anthryl group
₆~ C₁₄Having one or more substituents selected from the aryl groups of
You may have. R⁸C represented by₁~ C_FiveWith an alkyl group of
Then R², R^FourAnd R⁶As defined in
Similar groups are mentioned, C₇~ C₂₀As an aralkyl group of
Is a benzyl group, a 1-phenethyl group, a 2-phenethyl group,
1-phenylpropyl group, 2-phenylpropyl group, 3
-Phenylpropyl group, 4-phenylbutyl group, 5-phenyl group
Phenylpentyl group, 1-naphthylmethyl group, 2-naphthyl
Group, 1- (1-naphthyl) ethyl group, 1- (2
-Naphthyl) ethyl group, 2- (1-naphthyl) ethyl
Group, a 2- (2-naphthyl) ethyl group, and the like. R⁷And R⁸C formed together by₃~
C₁₅The cycloalkyl group of R is R^TenDefined in
And the same groups as. R⁹C defined by₆~ C₁₄
The aryl group of R is^TenA group similar to that defined in
Is mentioned. C defined by X₁~ C_FiveAlkylchi
O group, C₂~ C₆An alkoxycarbonylamino group of C
₁~ C_FiveMonoalkylamino group, C₂~ C_TenThe dial
Kiramino group, C₂~ C₆Acylamino group, C₁~ C
_FiveThe alkoxy group of is R³And R^FiveAt C₁~ C₂₀The al
Examples include groups similar to those defined as substituents for the kill group.
A heterocyclic residue, C₆~ C₁₄Aryl group of C₆~ C₁₄
As the aryloxy group of R^TenSame as defined in
Groups. R¹¹C defined by₁~ C₂₀Alkyl group of
As R^TenExamples include groups similar to those defined in
Such an alkyl group is a hydroxyl group; a mercapto group;
Mino group; benzylthio group, 1-phenylethylthio group,
2-phenylethylthio group, 1-naphthylmethylthio group
Group, C such as 2-naphthylmethylthio group₇~ C₂₀Aral
Kirthio group; each R³Or R^FiveAt C₁~ C₂₀of
The same C as defined as the substituent of the alkyl group₁~
C_FiveAlkoxy group of C₁~ C_FiveAlkylthio group of C
₁~ C_FiveMonoalkylamino group, C₂~ C_TenThe dial
Kiramino group; each is R^TenSimilar to that defined in
C₆~ C₁₄Aryloxy group, C₇~ C₂₀Aralchi
Luoxy group, C₆~ C₁₄Arylthio group, heterocyclic residue
It may have one or more substituents selected from Also, R⁹And R¹¹Form together
As the nitrogen-containing heterocycle, a pyrrolidine ring, a piperidine ring,
Piperazine ring, 1,2,3,4-tetrahydroquinoline
Ring, 1,2,3,4-tetrahydroisoquinoline ring,
-Hydroquinoline ring, perhydroisoquinoline ring, etc.
It has 1 to 4 terror atoms and the total number of atoms constituting the ring is 5
There are 10 types. Substituents on such a heterocycle
It may exist. Further, in the above definition, the position at the end of each substituent is
Aryl ring, partially hydrogenated aryl group and
Heterocycle is a fluorine atom, chlorine atom, bromine atom, or other
Rogen atom; methyl group, ethyl group, propyl group, isop
Ropyl group, butyl group, isobutyl group, sec-butyl
Group, tert-butyl group, pentyl group, isopentyl group
Group, C such as neopentyl group₁~ C_FiveAlkyl group of tri
Fluoromethyl group; methoxy group, ethoxy group, propoxy group
Si group, isopropoxy group, butoxy group, isobutoxy group
Group, tert-butoxy group, pentyloxy group, isopene
C such as an ethyloxy group₁~ C_FiveAlkoxy group of; methyle
Group, ethylenedioxy group, propylenedioxy group
C, such as Si group and butylenedioxy group₁~ C_FiveRing of aceta
Group; hydroxyl group; acetoxy group, propioni
Such as ruoxy group, butyryloxy group, valeryloxy group, etc.
C₂~ C₆Acyloxy group; formyl group; carboxy
Group; methoxycarbonyl group, ethoxycarbonyl group,
Propoxycarbonyl group, isopropoxycarbonyl
Group, butoxycarbonyl group, isobutoxycarbonyl
Group, tert-butoxycarbonyl group, pentyloxy
C such as carbonyl group₂~ C₆Alkoxycarbonyl
Group; oxo group; acetyl group, propionyl group, butyryl
Group, C such as valeryl group₂~ C₆An acyl group; an amino group;
Methylamino group, ethylamino group, propylamino group,
Isopropyl amino group, butyl amino group, isobutyl amino group
Mino group, tert-butylamino group, pentylamino
Group, C such as isopentylamino group₁~ C_FiveThe monoarch
Luamino group; dimethylamino group, ethylmethylamino
Group, diethylamino group, methylpropylamino group, diii
C such as Sopropylamino group₂~ C_TenDialkylamino
Group; acetylamino group, propionylamino group, isop
Ropionylamino group, butyrylamino group, isobutyryl
C such as amino group and valerylamino group₂~ C₆Asylor
Mino group; carbamoyl group; methylcarbamoyl group, ethyl
Rucarbamoyl group, propylcarbamoyl group, isopro
Pyrcarbamoyl group, butylcarbamoyl group, tert
-Butylcarbamoyl group, pentylcarbamoyl group, etc.
C₂~ C₆Alkylcarbamoyl group of phenyl group,
Ryryl group, 1-naphthyl group, 2-naphthyl group, anthryl
C etc.₆~ C₁₄An aryl group of; and R^TenDefined in
Having one or more substituents selected from heterocyclic residues similar to
You may have. [0032] [Chemical 11] (R¹¹Is C which may have a substituent₁~
C₁₅Represents an alkyl group. ) Is preferred,
Especially R⁹Is-(CH₂) m-X (X is a hydroxyl group, C
₁~ C_FiveAlkylthio group of C₂~ C₆Alkoxyka
Rubonylamino group, a heterocyclic residue which may have a substituent
Group, amino group, C₁~ C_FiveMonoalkylamino group, C
₂~ C_TenDialkylamino group of C₂~ C₆Asylor
Mino group, halogen atom, C₁~ C_FiveThe alkoxy group of
C which may have a substituent₆~ C₁₄An aryl group or
C which may have a substituent₆~ C₁₄Aryloxy
Represents a group, and m represents an integer of 1 to 10. ) Represents a compound
Is more preferable. An even more preferred compound is [0034] [Chemical 12] (R^TenIs C as a substituent₃~ C₁₅The cyclo
Alkyl group, C₃~ C₁₅Cycloalkenyl groups and substituents
May have C₆~ C₁₄Aryl group and substituent
C which may have_Ten~ C₁₄Partly hydrogenated ants
Group, a heterocyclic residue which may have a substituent, C₃~
C₁₅Cycloalkyloxy group, even if it has a substituent
Good C₆~ C₁₄Having an aryloxy group, a substituent of
May be C₆~ C₁₄Partially hydrogenated aryloki
Si group, optionally substituted heterocyclic oxy group, substituted
C which may have a group₇~ C₂₀Aralkyloxy groups
And optionally substituted C₆~ C₁₄Aryl
It may have one or more substituents selected from thio groups.
C₁~ C₁₅Alkyl group of C₃~ C₁₅Cycloalkyl
Group; C which may have a substituent₆~ C₁₄Aryl
Group; C which may have a substituent₆~ C₁₄Part of hydrogenation
Added aryl group; C which may have a substituent₂~
C_TenAn alkenyl group or a compound which may have a substituent
Represents a ring residue. ), R^FourAnd R⁶Respectively
Independently hydrogen atom or C₁~ C_FiveThe alkyl group of
And R^FiveIs a hydrogen atom or C which may have a substituent₆~
C₁₄Aryl group of C₁~ C_TenAlkoxy group or
C which may have a substituent₁~ C₁₅The alkyl group of
And R⁷Is C₃~ C₁₅Cycloalkyl group, hydroxy
Group, C optionally substituted with a heterocyclic residue₁~ C_Fiveof
Alkoxy group, C₆~ C₁₄Aryloxy group, C₇~
C₂₀Substituted with aralkyloxy groups, heterocyclic residues
May be C₁~ C_FiveAlkylthio group of C₆~ C₁₄A
Reelthio group, C₇~ C₂₀Aralkylthio group, carbo
Xyl group, carbamoyl group, C₂~ C₆Alkoxyka
One or more substitutions selected from a carbonyl group and a heterocyclic residue
C which may have a group₁~ C₁₅Alkyl group of hydrogen
Child; C which may have a substituent₆~ C₁₄Aryl group
Or C₁~ C_TenRepresents an alkoxy group of R⁸Is hydrogen
A compound that represents a child. The keto of the present invention represented by the above general formula (I)
Derivatives can form pharmaceutically acceptable salts.
Wear. Specific examples of such a salt include those where an acidic group is present.
, Lithium salt, sodium salt, potassium salt, mag
Metal salts such as nesium salt and calcium salt, or ammoni
Umium salt, methyl ammonium salt, dimethyl ammonium salt
Salt, trimethylammonium salt, dicyclohexylan
Can form ammonium salts such as monium salts,
Hydrochloride, hydrobromide, sulfate, if basic groups are present,
Mineral salts such as nitrates and phosphates, or methane sulfone
Acid salt, benzene sulfonate, paratoluene sulfonic acid
Salt, acetate, propionate, tartrate, fumaric acid
Salt, maleate, malate, oxalate, succinic acid
Salt, citrate, benzoate, mandelate, cinnamic acid
Organic acid salts such as salts and lactates can be formed. Ketone derivative represented by the above general formula (I)
Regarding the stereochemistry of the double bond site of (E),
The (Z) body or the (EZ) body can be taken. Well
In addition, the stereochemistry of the asymmetric carbon is
(R) body, (S) body, or (RS) body
it can. Component of the ketone derivative represented by the general formula (I)
As a physical example, when n = 0,
When the compound is n = 1, the compounds shown in Table 2 below are listed.
You can [0038] [Table 1][0039] [Table 2][0040] [Table 3][0041] [Table 4][0042] [Table 5][0043] [Table 6][0044] [Table 7][0045] [Table 8][0046] [Table 9][0047] [Table 10][0048] [Table 11][0049] [Table 12][0050] [Table 13][0051] [Table 14][0052] [Table 15][0053] [Table 16][0054] [Table 17][0055] [Table 18][0056] [Table 19][0057] [Table 20][0058] [Table 21][0059] [Table 22][0060] [Table 23][0061] [Table 24][0062] [Table 25][0063] [Table 26][0064] [Table 27][0065] [Table 28][0066] [Table 29][0067] [Table 30][0068] [Table 31][0069] [Table 32][0070] [Table 33][0071] [Table 34][0072] [Table 35][0073] [Table 36][0074] [Table 37][0075] [Table 38][0076] [Table 39][0077] [Table 40][0078] [Table 41][0079] [Table 42][0080] [Table 43][0081] [Table 44][0082] [Table 45][0083] [Table 46][0084] [Table 47][0085] [Table 48][0086] [Table 49][0087] [Table 50][0088] [Table 51][0089] [Table 52][0090] [Table 53][0091] [Table 54][0092] [Table 55][0093] [Table 56][0094] [Table 57][0095] [Table 58][0096] [Table 59][0097] [Table 60][0098] [Table 61][0099] [Table 62][0100] [Table 63][0101] [Table 64][0102] [Table 65][0103] [Table 66][0104] [Table 67][0105] [Table 68][0106] [Table 69][0107] [Table 70][0108] [Table 71][0109] [Table 72][0110] [Table 73][0111] [Table 74][0112] [Table 75][0113] [Table 76][0114] [Table 77][0115] [Table 78][0116] [Table 79][0117] [Table 80][0118] [Table 81][0119] [Table 82][0120] [Table 83][0121] [Table 84][0122] [Table 85][0123] [Table 86][0124] [Table 87][0125] [Table 88][0126] [Table 89][0127] [Table 90][0128] [Table 91][0129] [Table 92][0130] [Table 93][0131] [Table 94][0132] [Table 95][0133] [Table 96][0134] [Table 97][0135] [Table 98][0136] [Table 99][0137] [Table 100][0138] [Table 101][0139] [Table 102][0140] [Table 103][0141] [Table 104][0142] [Table 105][0143] [Table 106][0144] [Table 107][0145] [Table 108][0146] [Table 109][0147] [Table 110][0148] [Table 111][0149] [Table 112][0150] [Table 113][0151] [Table 114][0152] [Table 115][0153] [Table 116][0154] [Table 117][0155] [Table 118][0156] [Table 119][0157] [Table 120][0158] [Table 121][0159] [Table 122][0160] [Table 123][0161] [Table 124][0162] [Table 125][0163] [Table 126][0164] [Table 127][0165] [Table 128][0166] [Table 129][0167] [Table 130][0168] [Table 131][0169] [Table 132][0170] [Table 133][0171] [Table 134][0172] [Table 135][0173] [Table 136][0174] [Table 137][0175] [Table 138][0176] [Table 139][0177] [Table 140][0178] [Table 141][0179] [Table 142][0180] [Table 143][0181] [Table 144][0182] [Table 145][0183] [Table 146][0184] [Table 147][0185] [Table 148][0186] [Table 149][0187] [Table 150][0188] [Table 151][0189] [Table 152][0190] [Table 153][0191] [Table 154][0192] [Table 155][0193] [Table 156][0194] [Table 157][0195] [Table 158][0196] [Table 159][0197] [Table 160][0198] [Table 161][0199] [Table 162][0200] [Table 163][0201] [Table 164][0202] [Table 165][0203] [Table 166][0204] [Table 167][0205] [Table 168][0206] [Table 169][0207] [Table 170][0208] [Table 171][0209] [Table 172][0210] [Table 173][0211] [Table 174][0212] [Table 175][0213] [Table 176][0214] [Table 177][0215] [Table 178]Next, a method for producing the compound of the present invention will be explained.
Reveal The ketone derivative of the present invention can be prepared, for example, by the following method.
Can be manufactured in. [Production method 1] [0217] [Chemical 13](In the above general formula, R^Four, R^Five，
R⁶, R⁷, R⁸And R⁹As already defined
, [0219] [Chemical 14] (R^TenAs already defined. ),
Boc represents a tert-butoxycarbonyl group.
You ) Methods known from literature (Chemical an
d Pharmaceutical Bulletin,
Volume 37, page 3108, 1989)
Chloromethyl represented by the above general formula (II)
Ketone derivative, diethyl ether, tetrahydrofuran
Amine, dioxane, ethyl acetate, methylene chloride, chloropho
Sodium hydroxide, potassium hydroxide,
Salts of sodium hydride, triethylamine, pyridine, etc.
R in the presence of a group⁹-React with mercaptan represented by SH
Then, the thiomethylketo represented by the general formula (III) is obtained.
A derivative is obtained. Next, the Boc group of compound (III)
The reaction conditions usually used, for example, hydrochloric acid water, hydrochloric acid-E
Tanol, hydrogen chloride-ethyl acetate, hydrogen chloride-dioxa
Deprotection with hydrogen chloride, hydrobromic acid, hydrogen bromide-acetic acid, etc.
And an amine represented by the above general formula (IV), or an amine
To obtain the salt. On the other hand, the unit represented by the general formula (V) is
The carboxyl group of the mino acid derivative was replaced with isobutyric chloroformate.
, Diphenylphosphoryl azide, dicyclohexylca
Condensing agents such as rubodiimide and carbonyldiimidazole
Activated with triethylamine, pyridine if necessary
Reacting compound (IV) obtained above in the presence of a base such as
The compound represented by the general formula (VI)
Can be obtained. In addition, compound (VI)
System, methylene chloride, methanol, ethanol, ethyl acetate
Sodium metaperiodate, water peroxide
With sulfur, peracetic acid, metachloroperbenzoic acid, etc.
Oxidation group to sulfoxide group or sulfone group
The compound represented by the general formula (VII) is obtained by
It [Production method 2] [0222] [Chemical 15] (In the above general formula, Boc, R^Four, R
^Five, R⁶, R⁷, R⁸, R⁹, R¹¹And R¹²Is already
As defined. ) Represented by the above general formula (II)
Chloromethylketone derivative with diethyl ether, tetra
Hydrofuran, dioxane, ethyl acetate, chloroform
Dissolve in methylene chloride or methylene chloride, [0224] [Chemical 16] When the amine represented by
A diaminoketone derivative represented by general formula (VIII) is obtained.
It Then, the compound (VIII) is prepared by the same method as the production method 1.
Deprotecting the Boc group of to lead to compound (IX)
Condensation with an amino acid derivative represented by the general formula (V)
Thus, the compound represented by the above general formula (X) was obtained.
Be done. [Manufacturing method 3] [0226] [Chemical 17](In the above general formula, Boc, R^Four, R
^Five, R⁶, R⁷, R⁸, R⁹And R¹²Is already defined
That's right. ) Methods known in the literature (Methods in
Enzymology, 80, 820, 198
With the above general formula (XI), which can be easily produced using
Diazomethyl ketone represented by chloroform, methyl chloride
Dissolves in a solvent such as ren, CuO, Rh₂(OAc)_FourTransition of etc.
In the presence of a transfer metal catalyst, R⁹Alcohol represented by -OH
By reacting the compound represented by the general formula (XII) above.
An oxymethyl ketone derivative is obtained. In this case,
Formula (XI) without the use of solvents such as loroform and methylene chloride
Compound of alcohol R⁹Dissolve directly in -OH to react
You can also do it. Next, by the same method as the manufacturing method 1,
Deprotect the Boc group of compound (XII) to give compound (XIII)
Derivation, and further amino acid derivation represented by the general formula (V)
When condensed with the body, it is represented by the above general formula (XIV).
A compound is obtained. [0229] [Chemical 18][0230] [Chemical 19](In the above general formula, Boc, R^Four, R
^Five, R⁶, R⁷, R⁸, R⁹, R^Ten, R¹¹And A is
As defined above. ) Manufacturing method 1, manufacturing method 2,
In the manufacturing method 3, instead of formula (V), formula (XV)
The above general formulas (XVI) to (XIV) produced using the compound of
The Boc group of the compound represented by
When deprotected by, the compound represented by the above general formula (XX)
The product or its salt is obtained. Then compound (XX) is chloro
Form, methylene chloride, ethyl acetate, dimethylformua
Dissolve in a normal organic solvent such as amide, triethylamine,
In the presence of an amine such as pyridine, [0232] [Chemical 20] Reaction with an acyl chloride represented by
Then, a compound represented by the above general formula (XXI) is obtained.
Similarly, to the compound represented by the general formula (XX), [0234] [Chemical 21] Reacting a chloroformic acid derivative represented by
And a compound represented by the general formula (XXII)^Ten
When an isocyanate represented by -NCO is reacted,
A compound represented by the general formula (XXIII) is obtained, [0236] [Chemical formula 22] Reaction with a sulfonyl chloride represented by
Then, a compound represented by the above general formula (XXIV) is obtained.
You can [0238] [Chemical formula 23] (In the above general formula, R², R³，
R^Four, R^Five, R⁶, R⁷, R⁸, R⁹And Boc are already
As defined in. ) Amino acid derivation represented by the above general formula (XXV)
The carboxyl group of the body is treated in the same manner as in the production method 1.
Activated with a condensing agent and, if necessary, the presence of a base
Below, the compound (XX) obtained in the above Production Method 4 is reacted.
Then, a compound represented by the above general formula (XXVI) is obtained.
A compound of formula (XXVI) was prepared in the same manner as described in Preparation method 1.
The compound of the general formula (XXVII) or
Can obtain its salt. Furthermore, the compound of formula (XXVII)
The product converts the amino group according to the method described in production method 4.
be able to. Manufacturing method 1, manufacturing method 2 and manufacturing method described above
In a series of operations of Method 3, Manufacturing Method 4 and Manufacturing Method 5,
It is necessary to protect or deprotect the functional groups present in each compound.
Although it may be necessary, these operations are
By applying the general method usually used in
The reaction can be easily performed. Such a compound of the present invention
For clinical application, as a carrier component of therapeutically effective components
The ratio to the above can be varied between 1% by weight and 90% by weight.
sell. For example, the compound of the present invention is a granule, a fine granule, a powder, a tablet.
Agent, hard capsule, soft capsule, syrup, emulsion,
Orally administered in the form of a suspension or solution,
Administered intravenously, intramuscularly or subcutaneously as an injection
Good. It can also be used as a suppository. Also,
It may be made into powder for injection and prepared before use. Sutra
Suitable for oral, enteral and parenteral use, pharmaceutical organic or inorganic solid
Body or liquid carrier or diluent to prepare the drug of the present invention
Can be used for When manufacturing solid formulations
Excipients used include, for example, lactose, sucrose, demp
, Talc, cellulose, dextrin, kaolin, charcoal
Calcium acid or the like is used. Made of liquid for oral administration
Agents, that is, emulsions, syrups, suspensions, liquids, etc.
Commonly used inert diluents such as water or vegetable oils
including. This formulation contains adjuvants other than inert diluents, eg
Wetting agents, suspension aids, sweeteners, fragrances, colorants or
Preservatives and the like can be included. Gelatin in liquid form
May be included in capsules of absorbable substances such as
Yes. For the production of parenteral preparations, that is, injections, suppositories, etc.
Examples of the solvent or suspending agent used include water and a
Pyrene glycol, polyethylene glycol, benzyl
Alcohol, ethyl oleate, lecithin, etc.
It Examples of bases used for suppositories include cocoa butter,
Examples include emulsified cacao butter, laurin butter, Witepsol and the like.
To be The preparation method of the preparation may be a conventional method. Clinical dose used by oral administration
In general, the compound of the present invention for adults is generally
The daily dose is 0.01 to 1000 mg, but the age and disease
It is more preferable to appropriately increase or decrease depending on the condition and symptoms. The above
The daily dose of the drug of the present invention may be administered once a day or at appropriate intervals.
May be administered in 2 or 3 divided doses daily
However, it may be administered intermittently. When used as an injection, an adult
On the other hand, as a compound of the present invention, a single dose of 0.001-10
It is preferable to administer 0 mg continuously or intermittently. [0244] EXAMPLES The present invention will be further described below with reference examples and examples.
However, the present invention is not limited to the gist thereof.
However, there are no restrictions due to these reference examples and examples.
Not something. Reference Example 1 (s) -3-tert-butoki
Cycarbonylamino-1-furfurylthio-2-hepta
Non production (S) -3-tert-butoxycarbonylamino-1
-Chlor-2-heptanone 6.54 g and furfurilume
3.11 g of lecaptan and 200 ml of tetrahydrofuran
And add 13 ml of 2N aqueous sodium hydroxide solution.
After stirring at room temperature for 17 hours, add sodium bicarbonate water and add ethyl acetate.
It was extracted with. Wash the extract with saturated saline and wash with magnesium sulfate.
After drying with um, it is filtered, concentrated, and subjected to silica gel column chromatography.
Graphography (Developing solvent: Hexa containing 10% ethyl acetate
The desired product (7.82 g) was obtained. Yield 92% NMR (CDCl₃, Δ): 0.89 (t, J = 6.6)
Hz, 3H), 1.20 to 1.95 (m, 6H), 1.
44 (s, 9H), 3.28 (d, J = 15Hz, 1
H), 3.39 (d, J = 15 Hz, 1H), 3.74
(S, 2H), 4.52 (m, 1H), 5.09 (m,
1H), 6.22 (d, J = 2.9 Hz, 1H), 6.
31 (m, 1H), 7.36 (m, 1H) Reference Example 2 (s) -3-amino-1-fur
Production of furylthio-2-heptanone hydrochloride (S) -3-tert-butoxyca obtained in Reference Example 1
Rubonylamino-1-furfurylthio-2-heptanone
Dissolve 7.8 g in 80 ml of ethyl acetate and add 4N chloride water.
Add 80 ml of element-containing ethyl acetate solution and stir at room temperature for 1 hour.
After stirring, 100 ml of hexane was added. Generated crystals
Was filtered and washed with hexane to obtain 5.93 g of the desired product.
It was Yield 93% NMR (DMSO-d₆, Δ): 0.87 (t, J =
6.8 Hz, 3 H), 1.16 to 1.40 (m, 4
H), 1.63 to 1.95 (m, 2H), 3.55
(D, J = 16 Hz, 1H), 3.70 (d, J = 16
Hz, 1H), 3.81 (s, 2H), 4.27 (m,
1H), 6.30 (m, 1H), 6.41 (m, 1
H), 7.61 (m, 1H), 8.29 (m, 3H) Example 1 (s) -3-((s) -2-t
ert-Butoxycarbonylamino-4-methylvaleri
Ruamino) -1-furfurylthio-2-heptanone (Table
-1 Compound No. 43) (S) -3-Amino-1-furfuri obtained in Reference Example 2
5.39 g of ruthio-2-heptanone hydrochloride and (s)-
tert-butoxycarbonyl leucine N-hydroxy
6.37 g of succinimide ester was added to 1 part of methylene chloride.
Dissolve in 50 ml, add 5.4 ml of triethylamine
After stirring at room temperature for 15 hours, 0.5N hydrochloric acid water 100m
1 was added, and the mixture was extracted with methylene chloride. Saturate the extract with water
Wash sequentially with sodium bicarbonate solution and saturated saline solution, and dry with magnesium sulfate.
After drying, filter and concentrate, silica gel column chromatograph
E (developing solvent 25% ethyl acetate in hexane)
The product was manufactured to obtain 8.49 g of the desired product. Yield: 96% IR (neat, cm^-1): 3350, 1700, 16
75,1660 NMR (CDCl₃, Δ: 0.90 to 1.0 (m, 9)
H), 1.15 to 1.75 (m, 8H), 1.45
(S, 9H), 1.80 to 1.95 (m, 1H), 3.
26 (d, J = 15 Hz, 1 H), 3.35 (d, J =
15Hz, 1H), 3.72 (s, 2H), 4.14
(M, 1H), 4.75 (m, 1H), 4.92 (d,
J = 8 Hz, 1 H), 6.22 (d, J = 3.1 Hz,
1H), 6.30 (m, 1H), 6.72 (d, J = 7)
Hz, 1H), 7.36 (m, 1H) Example 2 (s) -3-((s) -2-a
Mino-4-methylvalerylamino) -1-furfurylchi
O-2-heptanone hydrochloride (Compound No. 6 in Table-1
2) Production (S) -3-((s) -2-ter obtained in Example 1
t-butoxycarbonylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-2-heptanone 8.47
g dissolved in 25 ml of ethyl acetate and containing 4N hydrogen chloride
25 ml of ethyl acetate solution was added. Stir for 50 minutes at room temperature
After that, add 50 ml of hexane and filter the generated crystals.
It was washed with hexane to obtain 4.31 g of the desired product. Yield: 59% IR (KBr, cm^-1): 3300, 1698, 167
0 NMR (CD₃OD, δ): 0.88 to 1.18 (m,
9H), 1.27 to 2.03 (m, 9H), 3.41.
(D, J = 15 Hz, 1H), 3.50 (d, J = 15
Hz, 1H), 3.79 (s, 2H), 3.98 (m,
1H), 4.75 (dd, J = 4.2Hz, 9.3H)
z, 1H), 6.28 (d, J = 3.4Hz, 1H),
6.37 (m, 1H), 7.46 (m, 1H) Example 3 (s) -1-furfurylthio-
3-((s) -4-methyl-2-phenoxyacetyla
Minovalerylamino) -2-heptanone (compounds in Table-1
Manufacturing of product number 82) (S) -3-((s) -2-amino obtained in Example 2
-4-Methylvalerylamino) -1-furfurylthio-
2-heptanone hydrochloride 4.31 g of methylene chloride 1
Dissolve in 00 ml and cool to 0 ° C, then phenoxyacetyl
2.07 g of chloride and 3.2 ml of triethylamine
added. After stirring at 0 ° C for 30 minutes and at room temperature for 30 minutes,
Add 50 ml of 0.5N hydrochloric acid water and extract with methylene chloride.
It was The extract was washed successively with water, saturated aqueous sodium hydrogen carbonate and saturated brine.
Dried over magnesium sulfate, filtered and concentrated
Silica gel column chromatography (developing solvent 25
% Hexane containing ethyl acetate) and the desired product 3.96.
g was obtained. Yield: 74% IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.87 (t, J = 6.7)
Hz, 3H), 0.93 (d, J = 6.0 Hz, 6
H), 1.14 to 1.40 (m, 4H), 1.48 to
2.0 (m, 5H), 3.27 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.53 (s, 2H), 4.56 (m,
1H), 4.74 (m, 1H), 6.23 (m, 1
H), 6.30 (m, 1H), 6.59 (d, J = 7H
z, 1H), 6.90 to 7.10 (m, 4H), 6.2
5 to 6.40 (m, 3H) Example 4 (s) -1-furfurylsulf
Inyl-3-((s) -4-methyl-2-phenoxya
Cetylaminovalerylamino) -2-heptanone (Table-
Preparation of compound No. 1 of 1) (S) -1-furfurylthio-3-obtained in Example 3
((S) -4-methyl-2-phenoxyacetylamino
Valerylamino) -2-heptanone (176 mg)
Dissolved in 10 ml of water and 10 ml of water, metaperiodic acid
82 mg of sodium was added and reacted at room temperature for 48 hours.
After that, methanol was distilled off under reduced pressure, and saturated saline was added. Ku
It was extracted with loroform and the extract was washed with saturated saline.
After that, dry over sodium sulfate, filter, concentrate and
Kagel column chromatography (Developing solvent Hexa
Of the target compound (66 mg)
Obtained. Yield: 37% Melting point: 96 to 99 ° C IR (KBr, cm^-1): 3320, 1720, 169
0,1650 NMR (CDCl₃, Δ): 0.78 to 1.07 (m,
9H), 1.15 to 2.05 (m, 9H), 3.34 to
3.70 (m, 1H), 4.05 to 4.78 (m, 7
H), 6.40 (m, 1H), 6.47 (m, 1H),
6.80 to 7.18 (m, 5H), 7.20 to 7.40
(M, 2H), 7.43 (m, 1H) Example 5 (s) -1-furfurylsulfo
Nil-3-((s) -4-methyl-2-phenoxyacetate
Cylaminovalerylamino) -2-heptanone (Table-1
Compound No. 84) of (S) -1-furfurylthio-3-obtained in Example 3
((S) -4-methyl-2-phenoxyacetylamino
Valerylamino) -2-heptanone (150 mg)
Dissolve in 3 ml of thylene and cool to 0 ° C.
177 mg of perfume was added. 30 minutes at 0 ℃, 10:00 at room temperature
After reacting for 10 minutes, 10% aqueous potassium carbonate solution was added.
Extract with methylene chloride and wash the extract with saturated saline.
Dried over sodium sulfate, filtered, concentrated and filtered through silica gel.
Column chromatography (developing solvent hexane: vinegar
Purification with ethyl acetate = 2: 1) to obtain 130 mg of the desired product.
It was Yield: 80% Melting point: 120-121 ° C IR (KBr, cm^-1): 3300, 1730, 165
0 NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 9)
H), 1.15 to 2.05 (m, 9H), 3.97.
(D, J = 15 Hz, 1H), 4.28 (d, J = 15
Hz, 1H), 4.40 to 4.63 (m, 6H), 6.
42 (m, 1H), 6.58 (m, 1H), 6.82-
6.99 (m, 4H), 7.04 (t, J = 7, 4H
z, 1H), 7.22 to 7.40 (m, 2H), 7.4.
8 (m, 1H) Example 6 (s) -3-((s) -2-be
Ndyloxycarbonylamino-4-methylvalerylami
No) -1-furfuryloxy-4-phenyl-2-butane
Production of Non (Compound No. 452 of Table-1) N-benzyloxycarbonyl-L-leucyl-L-phen
Nylalanine diazomethylketone 314 mg
Dissolved in 2 ml of ril alcohol and 1 ml of methylene chloride
Then, 10 mg of rhodium (II) acetate dimer was added. room temperature
After stirring for 1 hour at room temperature, the solvent was distilled off under reduced pressure and the residue was washed with silica gel.
Rum chromatography (developing solvent hexane-acetic acid
(Chill) to obtain 27 mg of the desired product. Yield: 7.4% Melting point: 94-95 ° C IR (KBr, cm^-1): 3314, 3285, 173
8,1692,1653 NMR (CDCl₃, Δ): 0.89 (d, J = 6.0)
Hz, 6H), 1.35 to 1.70 (m, 3H), 2.
94 (dd, J = 14 Hz, 6.2 Hz, 1H), 3.
10 (dd, J = 14 Hz, 6.5 Hz, 1H), 3.
97 (d, J = 17 Hz, 1H), 4.12 (m, 1
H), 4.15 (d, J = 17 Hz, 1H), 4.44
(D, J = 13 Hz, 1H), 4.53 (d, J = 13
Hz, 1H), 4.90 to 5.05 (m, 2H), 5.
09 (s, 2H), 6.28 to 6.43 (m, 2H),
6.51 (d, J = 7.0 Hz, 1H), 7.08
(D, J = 7.1 Hz, 2H), 7.17 to 7.30
(M, 3H), 7.35 (s, 5H), 7.41 (m,
1H) Reference Examples 1 and 2 and Examples 1, 2, 3, 4, 5
The same operation as in Steps 6 and 6 was performed to produce the following compound.
The physical property values are shown below. Example 7 1-((s) -2-benzyloxy
Cycarbonylamino-4-methylvalerylamino) -3
-Furfurylthio-2-propanone (Compound number in Table-1
Production of No. 2) Melting point: 59 to 62 ° C IR (KBr, cm^-1): 3340, 1730, 169
2,1648 NMR (CDCl₃, Δ): 0.94 (d, J = 6.0)
Hz, 6H), 1.48 to 1.77 (m, 3H), 3.
24 (s, 2H), 3.72 (s, 2H), 4.10
4.35 (m, 3H), 4.95 to 5.11 (m, 1
H), 5.12 (s, 2H), 6.21 (d, J = 3.
1 Hz, 1H), 6.32 (m, 1H), 6.63
(M, 1H), 7.15 to 7.38 (m, 6H) Example 8 1-((s) -2-benzyloxy
Cycarbonylamino-4-methylvalerylamino) -3
-(3-Pyridylmethylthio) -2-propanone (Table-
Preparation of Compound No. 1 of 1) IR (neat, cm^-1): 3306, 1717, 16
66 NMR (CDCl₃, Δ): 0.93 (d, J = 5.8)
Hz, 6H), 1.42 to 1.79 (m, 3H), 3.
10 (s, 2H), 3.66 (s, 2H), 4.25
(D, J = 4.7 Hz, 2H), 4.28 (m, 1
H), 5.11 (s, 2H), 5.50 (d, J = 8.
2Hz, 1H), 6.93 (m, 1H), 7.18 ~
7.42 (m, 6H), 7.65 (d, J = 7.8H
z, 1H), 8.42 to 8.60 (m, 2H) Example 9 3-((s) -2-benzyloxy
Cycarbonylamino-4-methylvalerylamino) -1
-Furfurylthio-3-methyl-2-butanone (Table-1
Compound No. 15) of Melting point: 80 to 82 ° C IR (KBr, cm^-1): 3275, 1728, 168
4,1651 NMR (CDCl₃, Δ): 0.92 (d, J = 5.8)
Hz, 3H), 0.93 (d, J = 6.2Hz, 3
H), 1.44 (s, 3H), 1.46 (s, 3H),
1.57 to 1.77 (m, 3H), 3.37 (s, 2
H), 3.77 (s, 2H), 4.13 (m, 1H),
5.10 (s, 2H), 6.23 (d, J = 3.2H
z, 1H), 6.29 (m, 1H), 6.66 (s, 1
H), 7.32 to 7.42 (m, 6H) Example 10 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-4-methyl-2-penta
Production of Non (Compound No. 22 in Table-1) IR (neat, cm^-1): 3300, 1720, 17
05,1660 NMR (CDCl₃, Δ): 0.79 (d, J = 6.8)
Hz, 3H), 0.92 (d, J = 6.8Hz, 3
H), 0.93 (d, J = 5.0 Hz, 6H), 1.4
2-1.77 (m, 3H), 2.20 (m, 1H),
3.24 (d, J = 15 Hz, 1H), 3.31 (d,
J = 15 Hz, 1H), 3.70 (s, 2H), 4.2
5 (m, 1H), 4.78 (dt, J = 8.9 Hz,
4.6 Hz, 1H), 5.10 (s, 2H), 5.39
(D, J = 7.4 Hz, 1 H), 6.21 (d, J =
2.8 Hz, 1H), 6.28 (m, 1H), 6.73
(D, J = 8.9 Hz, 1H), 7.32 (s, 5
H), 7.35 (m, 1H) Example 11 (s) -1-furfurylthio
-4-Methyl-3-((s) -4-methyl-2-pheno
Xyacetylaminovalerylamino) -2-pentanone
Production of (Compound No. 24 in Table-1) IR (neat, cm^-1): 3300, 1720, 17
10,1650 NMR (CDCl₃, Δ): 0.82 (d, J = 6.9)
Hz, 3H), 0.91 to 0.96 (m, 9H), 1.
49 to 1.82 (m, 3H), 2.23 (m, 1H),
3.26 (d, J = 15 Hz, 1H), 3.34 (d,
J = 15 Hz, 1H), 3.72 (s, 2H), 4.5
3 (s, 2H), 4.60 (m, 1H), 4.78 (d
t, J = 8.8 Hz, 4.5 Hz, 1H), 6.23
(D, J = 2.7 Hz, 1H), 6.30 (m, 1
H), 6.75 (d, J = 8.7 Hz, 1H), 6.9
0 to 6.99 (m, 3H), 7.03 (m, 1H),
7.25 to 7.40 (m, 3H) Example 12 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-2-hexanone (Table-1
Compound No. 28) of IR (neat, cm^-1): 3350, 1710, 16
55 NMR (CDCl₃, Δ): 0.89 (t, J = 7.2)
Hz, 3H), 0.94 (d, J = 6.2 Hz, 6
H), 1.15 to 1.95 (m, 7H), 3.24.
(D, J = 15 Hz, 1H), 3.31 (d, J = 15)
Hz, 1H), 3.71 (s, 2H), 4.21 (m,
1H), 4.75 (m, 1H), 5.11 (s, 2)
H), 5.21 (d, J = 8 Hz, 1H), 6.22
(D, J = 2.9 Hz, 1H), 6.28 (m, 1
H), 6.65 (m, 1H), 7.30 to 7.35.
(M, 6H) Example 13 (s) -1-furfurylthio
-3-((s) -4-methyl-2-phenoxyacetyl
Aminovalerylamino) -2-hexanone (Table 1
Production of compound number 30) IR (neat, cm^-1): 3300, 1720, 16
Fifty NMR (CDCl₃, Δ): 0.78 to 1.05 (m,
9H), 1.17 to 1.95 (m, 7H), 3.27.
(D, J = 15 Hz, 1H), 3.34 (d, J = 15
Hz, 1H), 3.72 (s, 2H), 4.53 (m,
1H), 4.55 (s, 2H), 4.75 (m, 1
H), 6.23 (d, J = 3.0 Hz, 1H), 6.3
0 (m, 1H), 6.58 (d, J = 10Hz, 1
H), 6.85 to 7.15 (m, 3H), 7.23 to
7.37 (m, 4H) Example 14 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -5-methyl-1-methylthio-2-hexanone
Production of (Compound No. 32 in Table-1) Melting point: 96-97 ° C IR (KBr, cm^-1): 3220, 1725, 169
3,1640 NMR (CDCl₃, Δ): 0.93 to 1.0 (m, 1
2H), 1.35 to 1.75 (m, 6H), 2.06
(S, 3H), 3.20 (d, J = 14Hz, 1H),
3.48 (d, J = 14 Hz, 1H), 4.19 (m,
1H), 4.84 (m, 1H), 5.11 (s, 2)
H), 5.17 (m, 1H), 6.48 (d, J = 7H
z, 1H), 7.35 (s, 5H) Example 15 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-5-methyl-2-hexa
Production of Non (Compound No. 35 in Table-1) IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.92 (d, J = 5.0
Hz, 6H), 0.94 (d, J = 5.0Hz, 6
H), 1.38 to 1.79 (m, 6H), 3.25.
(D, J = 15 Hz, 1H), 3.33 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 4.19 (m,
1H), 4.77 (ddd, J = 6.7Hz, 6.7H)
z, 2.2 Hz, 1H), 5.11 (s, 2H), 5.
15 (d, J = 6.7 Hz, 1H), 6.22 (d, J
= 2.5 Hz, 1H), 6.29 (m, 1H), 6.4
9 (d, J = 6.7 Hz, 0.5 H), 6.59 (d,
J = 6.7 Hz, 0.5 H), 7.27 to 7.40.
(M, 6H) Example 16 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -1-methylthio-2-heptanone (Table 1
Production of compound number 37) Melting point: 80 to 82 ° C IR (KBr, cm^-1): 3320, 1720, 168
5,1643 NMR (CDCl₃, Δ): 0.83 to 1.0 (m, 9)
H), 1.18 to 2.05 (m, 9H), 2.07
(S, 3H), 3.20 (d, J = 14Hz, 1H),
3.36 (d, J = 14 Hz, 1H), 4.23 (m,
1H), 4.84 (m, 1H), 5.12 (s, 2
H), 5.16 (m, 1H), 6.56 (d, J = 8H
z, 1H), 7.35 (s, 5H) Example 17 (s) -3-benzyloxyca
Rubonylaminoacetylamino-1-furfurylthio-
Preparation of 2-heptanone (Compound No. 38 of Table-1) IR (neat, cm^-1): 3350, 1720, 17
15,1670 NMR (CDCl₃, Δ): 0.87 (d, J = 6.7)
Hz, 3H), 1.12 to 1.40 (m, 4H), 1.
55 (m, 1H), 1.85 (m, 1H), 3.26
(D, J = 15 Hz, 1H), 3.34 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 3.90 (d,
J = 4.3 Hz, 2H), 4.81 (m, 1H), 5.
13 (s, 2H), 5.54 (m, 1H), 6.21
(D, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 6.72 (d, J = 7.0 Hz, 1H), 7.2
7-7.41 (m, 6H) Example 18 (s) -3-((s) -2-
Benzyloxycarbonylaminopropionylamino)-
1-furfurylthio-2-heptanone (Compounds of Table-1
No. 39) manufacturing Melting point: 85-87 ° C IR (KBr, cm^-1): 3300, 1730, 169
0,1660 NMR (CDCl₃, Δ): 0.87 (d, J = 6.8)
Hz, 3H), 1.15 to 1.37 (m, 3H), 1.
39 (d, J = 7.0 Hz, 3H), 1.45 to 1.7
5 (m, 2H), 1.87 (m, 1H), 3.26
(D, J = 15 Hz, 1H), 3.33 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 4.26 (m,
1H), 4.75 (m, 1H), 5.12 (s, 2
H), 5.32 (m, 1H), 6.22 (d, J = 3.
2Hz, 1H), 6.29 (m, 1H), 6.61
(M, 1H), 7.30 to 7.36 (m, 6H) Example 19 (s) -3-((s) -2-
Benzyloxycarbonylamino-3-methylbutyryl
Mino) -1-furfurylthio-2-heptanone (Table-1
Compound No. 40) of Melting point: 115-116 ° C IR (KBr, cm^-1): 3280, 1715, 169
0,1630 NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.92 (d, J = 6.8Hz, 3
H), 0.97 (d, J = 6.8 Hz, 3H), 1.1
5 to 1.39 (m, 4H), 1.53 (m, 1H),
1.89 (m, 1H), 2.14 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1 H), 3.71 (s, 2 H), 4.02 (d
t, J = 8.2 Hz, 6.1 Hz, 1H), 4.78
(M, 1H), 5.11 (s, 2H), 5.38 (d,
J = 8.2 Hz, 1H), 6.21 (d, J = 2.6H
z, 1H), 6.29 (m, 1H), 6.56 (d, J
= 7.7 Hz, 1H), 7.27 to 7.42 (m, 6)
H) Example 20 (s) -3-((s) -2-
Benzyloxycarbonylaminovalerylamino) -1-
Furfurylthio-2-heptanone (Compound number in Table-1
41) Manufacturing Melting point: 95-96 ° C IR (KBr, cm^-1): 3280, 3260, 169
0, 1680, 1640 NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.93 (t, J = 7.2Hz, 3
H), 1.16 to 1.47 (m, 6H), 1.50
1.67 (m, 2H), 1.75 to 1.97 (m, 2
H), 3.27 (d, J = 15 Hz, 1H), 3.33
(D, J = 15 Hz, 1H), 3.71 (s, 2H),
4.19 (m, 1H), 4.77 (m, 2H), 5.1
1 (s, 2H), 5.30 (d, J = 7.1Hz, 1
H), 6.21 (d, J = 3.1 Hz, 1H), 6.3
0 (m, 1H), 6.59 (d, J = 7.1Hz, 1
H), 7.37 to 7.43 (m, 6H) Example 21 (s) -3-((s) -2-
Cyclohexylmethoxycarbonylamino-4-methyl
Valerylamino) -1-furfurylthio-2-heptano
(Compound No. 46 of Table-1) IR (neat, cm^-1): 3330, 1715, 16
60 NMR (CDCl₃, Δ): 0.93 (t, J = 6.9)
Hz, 3H), 0.94 (d, J = 3.9Hz, 6
H), 1.10 to 2.0 (m, 20H), 3.26
(D, J = 15 Hz, 1H), 3.34 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 3.87 (d,
J = 6.4 Hz, 2H), 4.13 (m, 1H), 4.
74 (m, 1H), 5.0 (d, J = 6.4Hz, 1
H), 6.21 (d, J = 2.6 Hz, 1H), 6.2
9 (m, 1H), 6.60 (d, J = 8Hz, 1H),
7.35 (m, 1H) Example 22 (s) -3-((s) -2-
Benzyloxycarbonylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-2-heptanone (Table-1
Compound No. 48) of IR (neat, cm^-1): 3300, 1710, 16
55 NMR (CDCl₃, Δ): 0.87 (t, J = 6.8)
Hz, 3H), 0.95 (d, J = 5.9Hz, 6
H), 1.15 to 2.0 (m, 9H), 3.26 (d,
J = 14 Hz, 1 H), 3.33 (d, J = 14 Hz,
1H), 3.72 (s, 2H), 4.20 (m, 1
H), 4.75 (m, 1H), 5.12 (s, 2H),
5.13 (m, 1H), 6.22 (m, 1H), 6.3
0 (m, 1H), 6.55 (d, J = 7Hz, 1H),
7.26 to 7.45 (m, 6H) Example 23 (s) -3-[(s) -2-
(2-Fluorobenzyloxycarbonylamino) -4-
Methylvalerylamino] -1-furfurylthio-2-he
Preparation of Ptanone (Compound No. 49 of Table-1) IR (neat, cm^-1): 3320, 1710, 16
55 NMR (CDCl₃, Δ): 0.87 (t, J = 5.8)
Hz, 3H), 0.94 (d, J = 5.6Hz, 6
H), 1.07 to 2.0 (m, 9H), 3.25 (d,
J = 14Hz, 1H), 3.32 (d, J = 14Hz,
1H), 3.71 (s, 2H), 4.13 (m, 1
H), 4.75 (m, 1H), 5.05 to 5.27.
(M, 3H), 6,22 (m, 1H), 6,29 (m,
1H), 6.53 (d, J = 9Hz, 1H), 6.98
~ 7.19 (m, 2H), 7.21 to 7.43 (m, 3)
H) Example 24 (s) -3-[(s) -2-
(4-Fluorobenzyloxycarbonylamino) -4-
Methylvalerylamino] -1-furfurylthio-2-he
Production of Ptanone (Compound No. 51 in Table-1) Melting point: 67-68 ° C IR (KBr, cm^-1): 3400, 3250, 172
5,1640 NMR (CDCl₃, Δ): 0.87 (t, J = 7.2)
Hz, 3H), 0.94 (d, J = 5.0Hz, 6
H), 1.10 to 2.0 (m, 9H), 3.27 (d,
J = 14Hz, 1H), 3.37 (d, J = 14Hz,
1H), 3.71 (s, 2H), 4.17 (m, 1
H), 4.76 (m, 1H), 5.07 (s, 2H),
5.15 (d, J = 7 Hz, 1H), 6.22 (d, J
= 2.9 Hz, 1H), 6,30 (m, 1H), 6,5
0 (d, J = 7 Hz, 1 H), 7.05 (t, J = 8.
6Hz, 2H), 7.30 to 7.45 (m, 3H) Example 25 (s) -3-[(s) -2-
(2-Cyanobenzyloxycarbonylamino) -4-me
Cylvalerylamino] -1-furfurylthio-2-hep
Production of Tanone (Compound No. 56 of Table-1) IR (neat, cm^-1): 3281, 1766, 17
12,1658 NMR (CDCl₃, Δ): 0.85 to 1.06 (m,
9H), 1.25 to 1.43 (m, 4H), 1.52
1.83 (m, 3H), 1.83 to 2.02 (m, 2)
H), 3.24 (d, J = 15 Hz, 1H), 3.33
(D, J = 15 Hz, 1H), 3.67 (s, 2H),
4.56 (m, 1H), 4.77 (m, 1H), 5.3
3 (s, 2H), 6.17 (d, J = 3.1Hz, 1
H), 6.23 (m, 1H), 6, 25 (d, J = 8.
3Hz, 1H), 7.28 (dd, J = 6.4Hz,
5.3 Hz, 1H), 7.36 (m, 1H), 7.43
Up to 7.65 (m, 3H), 7.90 (d, J = 7.3H)
z, 1H) Example 26 (s) -3-[(s) -2-
(3-Cyanobenzyloxycarbonylamino) -4-me
Cylvalerylamino] -1-furfurylthio-2-hep
Production of Tanone (Compound No. 57 in Table-1) IR (KBr, cm^-1): 3400, 3250, 222
0,1710,1630 NMR (CDCl₃, Δ): 0.87 (t, J = 6.6)
Hz, 3H), 0.95 (d, J = 5.3Hz, 6
H), 1.09 to 1.39 (m, 4H), 1.42
1.77 (m, 4H), 1.89 (m, 1H), 3.2
6 (d, J = 15 Hz, 1H), 3.34 (d, J = 1
5 Hz, 1H), 3.71 (s, 2H), 4.19
(M, 1H), 4.77 (m, 1H), 5.13 (s,
2H), 5.25 (d, J = 7.8Hz, 1H), 6.
21 (d, J = 3.1 Hz, 1 H), 6.30 (m, 1
H), 6.61 (d, J = 7.3 Hz, 1H), 7.2
6 (s, 1H), 7.35 (m, 1H), 7.45
(M, 1H), 7.51 to 7.63 (m, 2H) Example 27 (s) -3-[(s) -2-
(4-Cyanobenzyloxycarbonylamino) -4-me
Cylvalerylamino] -1-furfurylthio-2-hep
Production of Tanone (Compound No. 58 in Table-1) Melting point: 83-89 ° C IR (KBr, cm^-1): 3400, 3270, 222
0,1720,1700,1640 NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.95 (d, J = 6.2Hz, 6
H), 1.13 to 1.40 (m, 3H), 1.43 to
1.79 (m, 5H), 1.79 to 1.99 (m, 1
H), 3.26 (d, J = 15 Hz, 1H), 3.30.
(D, J = 15 Hz, 1H), 3.72 (s, 2H),
4.19 (m, 1H), 4.77 (m, 1H), 5.1
6 (s, 2H), 5.32 (d, J = 8.0 Hz, 1
H), 6.21 (d, J = 2.9 Hz, 1H), 6.3
0 (m, 1H), 6.55 (d, J = 7.6Hz, 1
H), 7.36 (m, 1H), 7.44 (d, J = 8.
3Hz, 2H), 7.65 (d, J = 8.3Hz, 2
H) Example 28 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-pyridylmeth)
Xycarbonylamino) valerylamino] -2-hepta
Production of Non (Compound No. 59 of Table-1) IR (neat, cm^-1): 3350, 1715, 16
60 NMR (CDCl₃, Δ): 0.86 (t, J = 6.7)
Hz, 3H), 0.95 (d, J = 3.8Hz, 6
H), 1.07 to 1.99 (m, 9H), 3.27.
(D, J = 15 Hz, 1H), 3.32 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 4.22 (m,
1H), 4.77 (m, 1H), 5.24 (s, 2
H), 5.32 (d, J = 8 Hz, 1H), 6.21
(D, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 6.63 (d, J = 7 Hz, 1H), 7.20-
7.40 (m, 3H), 7.69 (m, 1H), 8.5
8 (d, J = 3.1Hz, 1H) Example 29 (s) -3-((s) -2-
Cyclohexylcarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-2-heptanone (Table-
Production of compound No. 1 of 1) Melting point: 109 ° C (decomposition) IR (KBr, cm^-1): 3294, 1707, 163
7 NMR (CDCl₃, Δ): 0.87 (t, J = 7.0)
Hz, 3H), 0.98 (d, J = 6.7Hz, 3
H), 0.99 (d, J = 6.7 Hz, 3H), 1.1
1-1.75 (m, 13H), 1.75-1.99
(M, 6H), 2.10 (m, 1H), 3.26 (d,
J = 15Hz, 1H), 3.30 (d, J = 15Hz,
1H), 3.72 (s, 2H), 4.47 (m, 1
H), 4.71 (m, 1H), 5.90 (d, J = 8.
1 Hz, 1 H), 6.21 (d, J = 2.6 Hz, 1
H), 6.30 (m, 1H), 6.81 (d, J = 7.
6Hz, 1H), 7.36 (m, 1H) Example 30 (s) -1-furfurylthio
-3-((s) -4-methyl-2-phenylacetyla
Minovalerylamino) -2-heptanone (compounds in Table-1
Manufacturing of article number 66) IR (neat, cm^-1): 3260, 1710, 16
35 NMR (CDCl₃, Δ): 0.75 to 1.07 (m,
9H), 1.13 to 1.99 (m, 9H), 3.20 to
3.38 (m, 2H), 3.59 (s, 2H), 3.7
1 (s, 2H), 4.43 (m, 1H), 4.68
(M, 1H), 5.78 (d, J = 8Hz, 1H),
6.21 (d, J = 3.2 Hz, 1H), 6.29
(M, 1H), 6.62 (d, J = 7.4Hz, 1
H), 7.16 to 7.40 (m, 6H) Example 31 (s) -3-[(s) -2-
(4-Fluorophenylacetylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 69 in Table-1) IR (neat, cm^-1): 3300, 1715, 16
60,1640 NMR (CDCl₃, Δ): 0.76 to 0.97 (m,
9H), 1.07 to 1.96 (m, 9H), 3.20 to
3.35 (m, 2H), 3.55 (d, J = 4.3H
z, 2H), 3.71 (s, 2H), 4.46 (m, 1
H), 4.71 (m, 1H), 5.85 (d, J = 7H
z, 1H), 6.20 (d, J = 3.0Hz, 1H),
6.29 (m, 1H), 6.59 (d, J = 6Hz,
0.6H), 6.69 (d, J = 6Hz, 0.4H),
7.03 (t, J = 8.6 Hz, 2H), 7.17-
7.35 (m, 3H) Example 32 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2,3-methylene
Dioxyphenylacetylamino) valerylamino]-
Preparation of 2-heptanone (Compound No. 73 of Table-1) IR (neat, cm^-1): 3280, 1720, 16
40 NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 9)
H), 1.13 to 1.98 (m, 9H), 3.20 to
3.37 (m, 2H), 3.55 (d, J = 3.9H
z, 2H), 3.71 (s, 2H), 4.44 (m, 1)
H), 4.70 (m, 1H), 5.90 to 6.07.
(M, 3H), 6.21 (d, J = 3.1 Hz, 1
H), 6.29 (m, 1H), 6.65 (d, J = 7H
z, 1H), 6.70 to 6.93 (m, 3H), 7.3.
5 (m, 1H) Example 33 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (1-naphthylacetate
Cylamino) valerylamino] -2-heptanone (Table-
Preparation of Compound No. 1 of No. 1) IR (neat, cm^-1): 3300, 1710, 16
40 NMR (CDCl₃, Δ): 0.70 (d, J = 6.5)
Hz, 3H), 0.72 (d, J = 6.5Hz, 3
H), 0.85 (t, J = 7.2 Hz, 3H), 1.0
5 to 1.91 (m, 9H), 3.20 to 3.38 (m,
2H), 3.70 (s, 2H), 4.02 (d, J = 1)
1Hz, 1H), 4.10 (d, J = 11Hz, 1
H), 4.39 (m, 1H), 4.63 (m, 1H),
5.59 (d, J = 8 Hz, 1H), 6.21 (d, J
= 2.9 Hz, 1H), 6.36 (m, 1H), 6.5
5 (d, J = 7 Hz, 0.5 H), 6.62 (d, J =
7 Hz, 0.5 H), 7.30 to 7.61 (m, 5
H), 7.80 to 8.0 (m, 3H) Example 34 (s) -3-[(s) -2-
(3-Benzothienylacetylamino) -4-methylva
Relylamino] -1-furfurylthio-2-heptanone
Production of (Compound No. 79 of Table-1) IR (neat, cm^-1): 3300, 1715, 16
40 NMR (CDCl₃, Δ): 0.71 to 1.0 (m, 9)
H), 1.07 to 1.97 (m, 9H), 3.24.
(D, J = 3.7 Hz, 0.7 H), 3.27 (d, J
= 3.0 Hz, 1.3 H), 3.70 (s, 1.3
H), 3.71 (s, 0.7H), 3.84 (s, 1.
3H), 3.85 (s, 0.7H), 4.40 (m, 1
H), 4.67 (m, 1H), 5.91 (m, 1H),
6.20 (d, J = 3.2 Hz, 1H), 6.29
(M, 1H), 6.57 (d, J = 6Hz, 0.7
H), 6.70 (d, J = 6 Hz, 0.3 H), 7.3
4 to 7.45 (m, 4H), 7.71 (m, 1H),
7.87 (m, 1H) Example 35 (s) -3-((s) -2-
Cyclohexyloxyacetylamino-4-methylvale
Rylamino) -1-furfurylthio-2-heptanone
Production of (Compound No. 81 in Table-1) IR (neat, cm^-1): 3400, 3300, 17
15,1665 NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 1
1H), 1.10 to 1.99 (m, 17H), 3.29
~ 3.40 (m, 3H), 3.71 (s, 0.7H),
3.72 (s, 1.3H), 3.98 (d, J = 1.0)
Hz, 1.3H), 3.99 (s, 0.7H), 4.5
0 (m, 1H), 4.74 (m, 1H), 6.22
(D, J = 2.7 Hz, 1H), 6.30 (m, 1
H), 6.70 (d, J = 7Hz, 0.7H), 6.7
7 (d, J = 7 Hz, 0.3 H), 6.92 (d, J =
8Hz, 1H), 7.35 (m, 1H) Example 36 (s) -3-[(s) -2-
(2-Fluorophenoxyacetylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 85 of Table-1) Melting point: 60 to 62 ° C IR (KBr, cm^-1): 3340, 1715, 167
0,1640 NMR (CDCl₃, Δ): 0.87 (t, J = 7.0)
Hz, 3H), 0.95 (d, J = 6.1Hz, 6
H), 1.10 to 1.99 (m, 9H), 3.26
(D, J = 15 Hz, 1H), 3.34 (d, J = 15
Hz, 1H), 3.72 (s, 2H), 4.53 (m,
1H), 4.57 (s, 2H), 4.75 (m, 1
H), 6.22 (d, J = 2.8 Hz, 1H), 6.2
9 (m, 1H), 6.65 (d, J = 8Hz, 1H),
6.90 to 7.20 (m, 5H), 7.36 (m, 1
H) Example 37 (s) -3-[(s) -2-
(3-Fluorophenoxyacetylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 86 of Table-1) IR (neat, cm^-1): 3300, 1750, 16
Fifty NMR (CDCl₃, Δ): 0.87 (t, J = 7.2)
Hz, 3H), 0.93 (d, J = 6.3Hz, 6
H), 1.15 to 2.0 (m, 9H), 3.20 to 3.
40 (m, 2H), 3.71 (d, J = 6.4 Hz, 2
H), 4.51 (d, J = 2.2 Hz, 2H), 4.6
1 (m, 1H), 4.76 (m, 1H), 6.21
(D, J = 3.1 Hz, 1 H), 6.28 (m, 1
H), 6.62 to 6.79 (m, 3H), 6.81
7.10 (m, 2H), 7.18 to 7.39 (m, 2
H) Example 38 (s) -3-[(s) -2-
(4-Fluorophenoxyacetylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 87 of Table-1) Melting point: 88 to 91 ° C IR (KBr, cm^-1): 3300, 1700, 164
0 NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.93 (d, J = 5.7Hz, 6
H), 1.10-2.0 (m, 9H), 3.21-3.
32 (m, 2H), 3.71 (d, J = 5.6Hz, 2
H), 4.48 (d, J = 2.7 Hz, 2H), 4.5
9 (m, 1H), 4.76 (m, 1H), 6.20
(D, J = 3.1 Hz, 1 H), 6.27 (m, 1
H), 6.65 (m, 1H), 6.78 to 7.10.
(M, 5H), 7.30 to 7.42 (m, 1H) Example 39 (s) -3-[(s) -2-
(2-chlorophenoxyacetylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 88 of Table-1) IR (neat, cm^-1): 3320, 1715, 16
Fifty NMR (CDCl₃, Δ): 0.85 (t, J = 3.9)
Hz, 3H), 0.92 to 1.05 (m, 6H), 1.
15-1.98 (m, 9H), 3.27 (d, J = 15)
Hz, 1H), 3.35 (d, J = 15Hz, 1H),
3.71 (s, 2H), 4.54 (s, 2H), 4.5
2 (m, 1H), 4.75 (m, 1H), 6.22
(M, 1H), 6.29 (m, 1H), 6.79 to 7.
05 (m, 3H), 7.17 to 7.31 (m, 2H),
7.33-7.45 (m, 2H) Example 40 (s) -3-[(s) -2-
(4-chlorophenoxyacetylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 90 of Table-1) Melting point: 66 to 67 ° C IR (KBr, cm^-1): 3320, 1710, 164
5 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.92 (d, J = 7.4Hz, 6
H), 1.07 to 1.99 (m, 9H), 3.23 to
3.38 (m, 2H), 3.72 (d, J = 5.0H
z, 2H), 4.50 (d, J = 3.2Hz, 2H),
4.53 (m, 1H), 4.76 (m, 1H), 6.2
0 (m, 1H), 6.28 (m, 1H), 6.57
(D, J = 8 Hz, 0.5 H), 6.70 (d, J = 8
Hz, 0.5H), 6.79 to 6.99 (m, 4H),
7.29 (d, J = 1.5 Hz, 1H), 7.36
(M, 1H) Example 41 (s) -3-[(s) -2-
(2,3-Dichlorophenoxyacetylamino) -4-
Methylvalerylamino] -1-furfurylthio-2-he
Production of Ptanone (Compound No. 91 in Table-1) Melting point: 79-80 ° C IR (KBr, cm^-1): 3300, 1715, 166
0,1645 NMR (CDCl₃, Δ): 0.87 (t, J = 7.0)
Hz, 3H), 0.94 (d, J = 5.2Hz, 3
H), 0.96 (d, J = 5.5 Hz, 3H), 1.1
0 to 2.0 (m, 9H), 3.23 to 3.40 (m, 2)
H), 3.72 (d, J = 3.6 Hz, 2H), 4.5
1 (m, 1H), 4.57 (s, 2H), 4.75
(M, 1H), 6.21 (m, 1H), 6.29 (m,
1H), 6.58 (d, J = 7Hz, 0.7H), 6.
70 (d, J = 7 Hz, 0.3 H), 6.82 (m, 1
H), 7.10 to 7.22 (m, 3H), 7.35.
(D, J = 1.9Hz, 1H) Example 42 (s) -3-[(s) -2-
(2,4-dichlorophenoxyacetylamino) -4-
Methylvalerylamino] -1-furfurylthio-2-he
Production of Ptanone (Compound No. 92 in Table-1) Melting point: 107-108 ° C IR (KBr, cm^-1): 3300, 1715, 166
0,1640 NMR (CDCl₃, Δ): 0.87 (t, J = 7.1)
Hz, 3H), 0.93 to 0.98 (m, 6H), 1.
05-1.99 (m, 9H), 3.27 (d, J = 14)
Hz, 1H), 3.36 (d, J = 14Hz, 1H),
3.70 (s, 0.4H), 3.72 (s, 1.6
H), 4.52 (m, 1H), 4.54 (s, 2H),
4.78 (m, 1H), 6.21 (d, J = 3.1H)
z, 1H), 6.30 (m, 1H), 6.58 (d, J
= 7 Hz, 0.8 H), 6.70 (d, J = 7 Hz,
0.2H), 6.84 (d, J = 9Hz, 1H), 7.
08-7.50 (m, 4H) Example 43 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2,4,6-tri
Chlorophenoxyacetylamino) valerylamino]-
Preparation of 2-heptanone (Compound No. 94 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
40 NMR (CDCl₃, Δ): 0.82 to 0.89 (m,
3H), 0.92 to 1.10 (m, 6H), 1.17 to
2.0 (m, 9H), 3.22 to 3.40 (m, 2
H), 3.70 (s, 0.4H), 3.72 (s, 1.
6H), 4.51 (d, J = 1.6Hz, 2H), 4.
63 (m, 1H), 4.76 (m, 1H), 6.21
(D, J = 2.6 Hz, 1H), 6.28 (m, 1
H), 6.83 (d, J = 7Hz, 0.8H), 6.9
2 (d, J = 7 Hz, 0.2 H), 7.23 to 7.40
(M, 4H) Example 44 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-methylpheno
Xyacetylamino) valerylamino] -2-heptano
(Compound No. 96 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.94 (d, J = 6.1Hz, 6
H), 1.07 to 1.97 (m, 9H), 2.30.
(S, 3H), 3.19 to 3.39 (m, 2H), 3.
71 (d, J = 4.6 Hz, 2H), 4.53 (d, J
= 1.8 Hz, 2H), 4.54 (m, 1H), 4.7
6 (m, 1H), 6.22 (m, 1H), 6.30
(M, 1H), 6.55 to 6.82 (m, 2H), 6.
87-7.03 (m, 2H), 7.11-7.21
(M, 2H), 7.30 to 7.40 (m, 1H) Example 45 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (3-methylpheno
Xyacetylamino) valerylamino] -2-heptano
(Compound No. 97 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.78 to 1.01 (m,
9H), 1.05 to 1.95 (m, 9H), 2.33
(S, 3H), 3.21 to 3.38 (m, 2H), 3.
70 (s, 1.3H), 3.72 (s, 0.7H),
4.50 (s, 0.7H), 4.51 (s, 1.3
H), 4.56 (m, 1H), 4.73 (m, 1H),
6.20 (m, 1H), 6.28 (m, 1H), 6.5
8 to 6.80 (m, 3H), 6.84 (d, J = 6.9)
Hz, 1H), 6.92 (d, J = 8.3Hz, 1
H), 7.19 (t, J = 7.7 Hz, 1H), 7.3
5 (m, 1H) Example 46 (s) -3-[(s) -2-
(4-chloro-2-methylphenoxyacetylamino)
-4-Methylvalerylamino] -1-furfurylthio-
Preparation of 2-heptanone (Compound No. 100 of Table-1) IR (neat, cm^-1): 3300, 1715, 16
Fifty NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.95 (d, J = 5.3Hz, 6
H), 1.19 to 1.99 (m, 9H), 2.25.
(S, 3H), 3.22 to 3.38 (m, 2H), 3.
71 (d, J = 5.9 Hz, 2H), 4.49 (s, 2
H), 4.60 (q, J = 7.6 Hz, 1H), 4.7
8 (m, 1H), 6.20 (m, 1H), 6.27
(M, 1H), 6.63 to 6.80 (m, 1.5H),
6.82-7.20 (m, 3.5H), 7.35 (m,
1H) Example 47 (s) -1-furfurylthio
-3-[(s) -2- (2-methoxyphenoxyacetyl)
Lumino) -4-methylvalerylamino] -2-hepta
Production of Non (Compound No. 102 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.85 (t, J = 7.1)
Hz, 3H), 0.91 (d, J = 6.2Hz, 3
H), 0.93 (d, J = 6.2 Hz, 3H), 1.0
7 to 1.37 (m, 5H), 1.42 to 1.63 (m,
2H), 1.63 to 1.95 (m, 2H), 3.25.
(D, J = 15 Hz, 1H), 3.33 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 3.88 (s,
3H), 4.50 (m, 1H), 4.56 (s, 2
H), 4.70 (m, 1H), 6.22 (d, J = 2.
9Hz, 1H), 6.30 (m, 1H), 6.74
(D, J = 7.6 Hz, 1H), 6.84 to 7.0
(M, 3H), 7.05 (m, 1H), 7.35 (m,
1H), 7.47 (d, J = 8.0Hz, 1H) Example 48 (s) -1-furfurylthio
-3-[(s) -2- (4-methoxyphenoxyacetyl)
Lumino) -4-methylvalerylamino] -2-hepta
Production of Non (Compound No. 104 of Table-1) Melting point: 86 to 88 ° C IR (KBr, cm^-1): 3302, 3261, 171
2,1668,1637 NMR (CDCl₃, Δ): 0.86 (t, J = 6.9)
Hz, 3H), 0.94 (d, J = 6.0 Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.45
1.78 (m, 4H), 1.89 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 3.77
(S, 3H), 4.43 (d, J = 10Hz, 1H),
4.48 (d, J = 10 Hz, 1H), 4.61 (m,
1H), 4.74 (m, 1H), 6.22 (d, J =
3.1 Hz, 1H), 6.30 (m, 1H), 6.80
~ 6.91 (m, 5H), 7.01 (d, J = 8.4H
z, 1H), 7.36 (m, 1H) Example 49 (s) -1-furfurylthio
-3-((s) -4-methyl-2-phenylthioacetyl
Ruaminovalerylamino) -2-heptanone (Table 1
Production of compound number 107) IR (neat, cm^-1): 3300, 1715, 16
40 NMR (CDCl₃, Δ): 0.78 to 1.05 (m,
9H), 1.15 to 2.05 (m, 9H), 3.18 to
3.27 (m, 2H), 3.57 to 3.75 (m, 4
H), 4.50 (m, 1H), 4.69 (m, 1H),
6.21 (d, J = 2.4 Hz, 1H), 6.29
(M, 1H), 6.68 (d, J = 8Hz, 0.4
H), 6.81 (d, J = 8Hz, 0.6H), 7.0
8 to 7.40 (m, 7H) Example 50 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (3-phenoxypi)
Ropionylamino) valerylamino] -2-heptanone
Production of (Compound No. 109 in Table-1) IR (neat, cm^-1): 3300, 1715, 16
40 NMR (CDCl₃, Δ): 0.83 (t, J = 6.8)
Hz, 3H), 0.90 to 0.94 (m, 6H), 1.
10 to 1.99 (m, 9H), 2.66 (t, J = 5.
9Hz, 1H), 2.69 (t, J = 5.9Hz, 1
H), 3.20 to 3.38 (m, 2H), 3.68.
(S, 1.3H), 3.70 (s, 0.7H), 4.2
5 (t, J = 5.9 Hz, 2H), 4.55 (m, 1
H), 4.70 (m, 1H), 6.20 (d, J = 3.
3Hz, 1H), 6.28 (m, 1H), 6.52
(D, J = 7 Hz, 1 H), 6.80 to 7.01 (m,
4H), 7.20 to 7.40 (m, 3H) Example 51 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (5,6,7,8-
Tetrahydro-1-naphthoxyacetylamino) valery
Lumino] -2-heptanone (Compound No. 11 in Table-1
1) production NMR (CDCl₃, Δ): 0.80 to 1.08 (m,
9H), 1.15-2.0 (m, 13H), 2.67-
2.80 (m, 4H), 3.21 to 3.40 (m, 2
H), 3.71 (d, J = 7.3 Hz, 2H), 4.4
9 (s, 2H), 4.60 (m, 1H), 4.76
(Q, J = 4.6 Hz, 1H), 6.20 (m, 1
H), 6.27 (m, 1H), 6.58 (d, J = 8H
z, 1H), 6.70 to 6.85 (m, 2H), 6.8.
7 to 7.10 (m, 2H), 7.35 (m, 1H) Example 52 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (1-naphthoxya
Cetylamino) valerylamino] -2-heptanone (Table
-1 Compound No. 114) IR (neat, cm^-1): 3300, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.80 to 0.98 (m,
9H), 1.10 to 2.0 (m, 9H), 3.28.
(D, J = 15 Hz, 1H), 3.35 (d, J = 15
Hz, 1H), 3.73 (s, 2H), 4.58 (m,
1H), 4.73 (s, 2H), 4.74 (m, 1
H), 6.22 (m, 1H), 6.29 (m, 1H),
6.63 (d, J = 7 Hz, 1H), 6.83 (d, J
= 7 Hz, 1 H), 7.01 (d, J = 7.1 Hz, 1
H), 7.32 to 7.60 (m, 5H), 7.83
(M, 1H), 8.21 (m, 1H) Example 53 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-naphthoxya
Cetylamino) valerylamino] -2-heptanone (Table
-1 Compound No. 115) Melting point: 87-89 ° C IR (KBr, cm^-1): 3270, 1700, 166
5,1640 NMR (CDCl₃, Δ): 0.78 to 1.0 (m, 9)
H), 1.05 to 1.98 (m, 9H), 3.21 to
3.40 (m, 2H), 3.69 (s, 0.2H),
3.72 (s, 1.8H), 4.50 to 4.70 (m,
1H), 4.62 (s, 2H), 4.74 (m, 1
H), 6, 22 (d, J = 3.1 Hz, 1H), 6.2
9 (m, 1H), 6.67 (d, J = 9Hz, 0.9
H), 6.80 (d, J = 9 Hz, 0.1H), 6.9
7 (d, J = 9 Hz, 1H), 7.12 to 7.93
(M, 8H) Example 54 (s) -3-((s) -2-
Benzoylamino-4-methylvalerylamino) -1-
Furfurylthio-2-heptanone (Compound number in Table-1
116) Production IR (neat, cm^-1): 3300, 1710, 16
Thirty NMR (CDCl₃, Δ): 0.83 (t, J = 6.7)
Hz, 1.5H), 0.89 (t, J = 6.7Hz,
1.5H), 1.01 (d, J = 5.8Hz, 6H),
1.15 to 2.0 (m, 9H), 3.28 (d, J = 1
5Hz, 0.5H), 3.30 (d, J = 15Hz,
0.5H), 3.36 (d, J = 15Hz, 0.5
H), 3.38 (d, J = 15 Hz, 0.5H), 3.
71 (s, 1H), 3.75 (s, 1H), 4.69-
4.84 (m, 2H), 6.21 (d, J = 2.5H
z, 0.5H), 6.24 (d, J = 2.5Hz, 0.
5H), 6.29 (m, 0.5H), 6.33 (m,
0.5H), 6.61 (d, J = 7Hz, 1H), 6.
76 (d, J = 7Hz, 0.5H), 6.82 (d, J
= 7 Hz, 0.5 H), 7.24 to 7.87 (m, 6
H) Example 55 (s) -3-[(s) -2-
(2-Fluorobenzoylamino) -4-methylvaleri
Lumino] -1-furfurylthio-2-heptanone (Table
-1 Compound No. 117) Melting point: 102-103 ° C IR (KBr, cm^-1): 3287, 1734, 163
5 NMR (CDCl₃, Δ): 0.81 (t, J = 6.7)
Hz, 3H), 0.97 (d, J = 5.6Hz, 3
H), 0.99 (d, J = 5.7 Hz, 3H), 1.1
5 to 1.40 (m, 4H), 1.51 to 1.65 (m,
1H), 1.65 to 1.82 (m, 3H), 1.90
(M, 1H), 3.27 (d, J = 15Hz, 1H),
3.35 (d, J = 15 Hz, 1 H), 3.72 (s,
2H), 4.63 to 4.82 (m, 2H), 6.23.
(D, J = 3.2 Hz, 1H), 6.30 (m, 1
H), 6.74 (d, J = 7.4 Hz, 1H), 7.0
4 (dd, J = 9.0 Hz, 7.6 Hz, 1 H), 7.
12 (dd, J = 12 Hz, 8.3 Hz, 1H), 7.
27 (d, J = 12 Hz, 1 H), 7.36 (m, 1
H), 7.48 (m, 1H), 8.07 (ddd, J =
7.8Hz, 7.8Hz, 1.7Hz, 1H) Example 56 (s) -3-[(s) -2-
(3-Fluorobenzoylamino) -4-methylvaleri
Lumino] -1-furfurylthio-2-heptanone (Table
-1 Compound No. 118) IR (KBr, cm^-1): 3285, 1734, 163
5 NMR (CDCl₃, Δ): 0.79 (t, J = 6.7)
Hz, 3H), 0.94 (d, J = 5.0Hz, 6
H), 1.13 to 1.38 (m, 4H), 1.43 to
1.63 (m, 1H), 1.64 to 1.97 (m, 4
H), 3.34 (s, 2H), 3.72 (s, 2H),
4.71 (m, 1H), 4.85 (m, 1H), 6.2
2 (d, J = 3.1 Hz, 1 H), 6.29 (m, 1
H), 7.16 (ddd, J = 8.3 Hz, 8.3H)
z, 2.4 Hz, 1H), 7.28 to 7.45 (m, 3
H), 7.50 to 7.62 (m, 3H) Example 57 (s) -3-[(s) -2-
(4-Fluorobenzoylamino) -4-methylvaleri
Lumino] -1-furfurylthio-2-heptanone (Table
-1 Compound No. 119) IR (KBr, cm^-1): 3315, 1716, 163
7 NMR (CDCl₃, Δ): 0.81 (t, J = 6.6
Hz, 3H), 0.98 (d, J = 5.5Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.57
(M, 1H), 1.62 to 1.82 (m, 3H), 1.
89 (m, 1H), 3.27 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.65 to 4.87 (m, 2H), 6.
22 (d, J = 3.1 Hz, 1 H), 6.30 (m, 1
H), 6.67 (d, J = 7.7 Hz, 1H), 6.7
5 (d, J = 7.7 Hz, 1 H), 7.11 (dd, J
= 8.7 Hz, 8.7 Hz, 2H), 7.36 (m, 1
H), 7.75 to 7.84 (m, 2H) Example 58 (s) -3-[(s) -2-
(2,3-Difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 120 of Table-1) Melting point: 120 to 122 ° C IR (KBr, cm^-1): 3285, 1734, 165
8,1635 NMR (CDCl₃, Δ): 0.82 (t, J = 6.6)
Hz, 3H), 0.98 (d, J = 6.0 Hz, 3
H), 0.99 (d, J = 6.2 Hz, 3H), 1.1
5 to 1.39 (m, 4H), 1.56 (m, 1H),
1.63 to 1.82 (m, 3H), 1.90 (m, 1
H), 3.27 (d, J = 15 Hz, 1H), 3.30.
(D, J = 15 Hz, 1H), 3.72 (s, 2H),
4.68 (m, 1H), 4.76 (m, 1H), 6.2
3 (d, J = 3.1 Hz, 1 H), 6.30 (m, 1
H), 6.64 (d, J = 7.4 Hz, 1H), 6.9
2 (d, J = 11 Hz, 0.5 H), 6.96 (d, J
= 11 Hz, 0.5 H), 7.17 to 7.40 (m, 4
H) Example 59 (s) -3-[(s) -2-
(2,4-difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 121 of Table-1) Melting point: 97-98 ° C IR (KBr, cm^-1): 3283, 1730, 165
8,1633 NMR (CDCl₃, Δ): 0.82 (t, J = 6.7)
Hz, 3H), 0.97 (d, J = 6.1 Hz, 3
H), 0.99 (d, J = 6.1 Hz, 3H), 1.1
7 to 1.39 (m, 4H), 1.57 (m, 1H),
1.61 to 1.82 (m, 3H), 1.89 (m, 1
H), 3.27 (d, J = 15 Hz, 1H), 3.35.
(D, J = 15 Hz, 1H), 3.73 (s, 2H),
4.69 (m, 1H), 4.77 (m, 1H), 6.2
2 (d, J = 3.2 Hz, 1H), 6.30 (m, 1
H), 6.67 (d, J = 7.3 Hz, 1H), 6.8
2 to 7.05 (m, 3H), 7.36 (m, 1H),
8.11 (m, 1H) Example 60 (s) -3-[(s) -2-
(2,5-Difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 122 of Table-1) Melting point: 102 ° C IR (KBr, cm^-1): 3283, 1734, 163
7 NMR (CDCl₃, Δ): 0.83 (t, J = 6.8)
Hz, 3H), 0.98 (d, J = 6.0 Hz, 3
H), 0.99 (d, J = 5.9 Hz, 3H), 1.1
7 to 1.37 (m, 4H), 1.49 to 1.82 (m,
4H), 1.90 (m, 1H), 3.27 (d, J = 1)
5Hz, 1H), 3.35 (d, J = 15Hz, 1
H), 3.73 (s, 2H), 4.69 (m, 1H),
4.77 (m, 1H), 6.22 (d, J = 3.2H
z, 1H), 6.30 (m, 1H), 6.64 (d, J
= 6.5 Hz, 1 H), 7.02 to 7.23 (m, 3
H), 7.35 (m, 1H), 7.75 (m, 1H) Example 61 (s) -3-[(s) -2-
(2,6-Difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 123 of Table-1) Melting point: 116 ° C IR (KBr, cm^-1): 3250, 1720, 167
0,1640,1620 NMR (CDCl₃, Δ): 0.87 (t, J = 6.7)
Hz, 3H), 0.99 (d, J = 5.8Hz, 6
H), 1.18 to 1.41 (m, 4H), 1.50
1.82 (m, 4H), 1.89 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.65
4.86 (m, 2H), 6.22 (d, J = 3.2H
z, 1H), 6.30 (m, 1H), 6.44 (d, J
= 8.0 Hz, 1H), 6.73 (d, J = 7.6H)
z, 1H), 6.95 (dd, J = 8.1Hz, 8.1
Hz, 2H), 7.31 to 7.43 (m, 2H) Example 62 (s) -3-[(s) -2-
(3,4-difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 124 of Table-1) Melting point: 94-100 ° C IR (KBr, cm^-1): 3315, 1720, 163
9,1602 NMR (CDCl₃, Δ): 0.79 (t, J = 7.0)
Hz, 3H), 0.86 (d, J = 5.1Hz, 6
H), 1.09 to 1.39 (m, 4H), 1.47 to
1.64 (m, 1H), 1.64 to 1.98 (m, 4
H), 3.34 (s, 2H), 3.73 (s, 2H),
4.72 (m, 1H), 4.85 (m, 1H), 6.2
2 (d, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 7.12 (ddd, J = 8.6Hz, 8.6H
z, 8.6 Hz, 1H), 7.35 (m, 1H), 7.
45 to 7.63 (m, 2H), 7.67 (m, 1H),
7.89 (m, 1H) Example 63 (s) -3-[(s) -2-
(3,5-difluorobenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 125 of Table-1) Melting point: 125-126 ° C IR (KBr, cm^-1): 3283, 1723, 163
7 NMR (CDCl₃, Δ): 0.84 (t, J = 6.7)
Hz, 3H), 0.97 (d, J = 6.1 Hz, 6
H), 1.17 to 1.40 (m, 4H), 1.54
(M, 1H), 1.64 to 1.82 (m, 3H), 1.
90 (m, 1H), 3.28 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.68 (m, 1H), 4.81 (m,
1H), 6.22 (d, J = 3.0Hz, 1H), 6.
31 (m, 1H), 6.66 (d, J = 7.6 Hz, 1
H), 6.85 (d, J = 8.2 Hz, 1H), 6.9
5 (m, 1H), 7.25 to 7.31 (m, 2H),
7.37 (m, 1H) Example 64 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2,3,4-tri
Fluorobenzoylamino) valerylamino] -2-f
Production of Ptanone (Compound No. 126 of Table-1) Melting point: 101 to 102 ° C IR (KBr, cm^-1): 3288, 1732, 166
0,1637 NMR (CDCl₃, Δ): 0.83 (t, J = 6.8)
Hz, 3H), 0.98 (d, J = 6.1Hz, 3
H), 0.99 (d, J = 6.1 Hz, 3H), 1.1
7 to 1.40 (m, 4H), 1.47 to 1.82 (m,
4H), 1.91 (m, 1H), 3.27 (d, J = 1)
5Hz, 1H), 3.35 (d, J = 15Hz, 1
H), 3.73 (s, 2H), 4.70 (m, 1H),
4.80 (m, 1H), 6.22 (d, J = 3.1H
z, 1H), 6.30 (m, 1H), 6.61 (d, J
= 6.0 Hz, 1H), 6.91 (d, J = 9.0H)
z, 0.5H), 6.95 (d, J = 9.0Hz, 0.
5H), 7.11 (m, 1H), 7.36 (m, 1
H), 7.83 (m, 1H) Example 65 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2,3,6-tri
Fluorobenzoylamino) valerylamino] -2-f
Production of Ptanone (Compound No. 128 of Table-1) Melting point: 116-117 ° C IR (KBr, cm^-1): 3281, 1734, 164
7 NMR (CDCl₃, Δ): 0.88 (t, J = 6.8)
Hz, 3H), 0.99 (d, J = 4.9Hz, 6
H), 1.18 to 1.42 (m, 4H), 1.50 to
1.82 (m, 4H), 1.92 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 4.71
(M, 1H), 4.81 (m, 1H), 6.22 (d,
J = 3.2 Hz, 1H), 6.30 (m, 1H), 6.
48 (d, J = 7.9 Hz, 1H), 6.64 (d, J
= 7.3 Hz, 1H), 6.92 (m, 1H), 7.2
5 (m, 1H), 7.36 (m, 1H) Example 66 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (3,4,5-tri
Fluorobenzoylamino) valerylamino] -2-f
Production of Ptanone (Compound No. 130 in Table-1) IR (KBr, cm^-1): 3298, 1716, 163
9 NMR (CDCl₃, Δ): 0.83 (t, J = 6.7)
Hz, 3H), 0.98 (d, J = 6.7Hz, 6
H), 1.13 to 1.39 (m, 4H), 1.47 to
1.80 (m, 4H), 1.91 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 4.70
(M, 1H), 4.78 (m, 1H), 6.22 (d,
J = 2.9 Hz, 1H), 6.30 (m, 1H), 6.
92 (d, J = 7.6 Hz, 1 H), 7.35 (m, 1
H), 7.41 to 7.59 (m, 3H) Example 67 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2,3,4,5-
Tetrafluorobenzoylamino) valerylamino]-
Preparation of 2-heptanone (Compound No. 132 of Table-1) Melting point: 107-108 ° C IR (KBr, cm^-1): 3277, 1705, 164
1 NMR (CDCl₃, Δ): 0.84 (t, J = 7.0)
Hz, 3H), 0.98 (d, J = 5.9Hz, 6
H), 1.15 to 1.38 (m, 4H), 1.43 to
1.80 (m, 4H), 1.90 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 4.67
(M, 1H), 4.81 (m, 1H), 6.22 (d,
J = 3.3 Hz, 1H), 6.30 (m, 1H), 6.
57 (d, J = 7.6 Hz, 1H), 6.99 (d, J
= 8.0 Hz, 0.5 H), 7.03 (d, J = 8.0)
Hz, 0.5H), 7.36 (m, 1H), 7.70
(M, 1H) Example 68 (s) -1-furfurylthio
-3-((s) -4-methyl-2-pentafluoroben
Zoylaminovalerylamino) -2-heptanone (Table-
Preparation of Compound No. 135 of 1) IR (KBr, cm^-1): 3287, 1714, 165
Three NMR (CDCl₃, Δ): 0.87 (t, J = 6.7)
Hz, 3H), 0.98 (d, J = 5.4Hz, 6
H), 1.12 to 1.39 (m, 4H), 1.45
1.79 (m, 4H), 1.80 to 1.98 (m, 1
H), 3.31 (s, 2H), 3.72 (s, 2H),
4.63 to 4.84 (m, 2H), 6.21 (d, J =
3.2 Hz, 1H), 6.30 (m, 1H), 6.68
(D, J = 7.8 Hz, 1H), 6.88 (d, J =
8.3 Hz, 1H), 7.35 (m, 1H) Example 69 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-toluoyl alcohol
Mino) valerylamino] -2-heptanone (Table 1
Production of compound number 140) Melting point: 118-119 ° C IR (KBr, cm^-1): 3275, 1734, 163
5 NMR (CDCl₃, Δ): 0.86 (t, J = 6.9)
Hz, 3H), 0.99 (d, J = 5.7Hz, 6
H), 1.17 to 1.40 (m, 4H), 1.44 to
1.80 (m, 4H), 1.91 (m, 1H), 2.4
4 (s, 3H), 3.72 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.74
(S, 2H), 4.65 (m, 1H), 4.80 (m,
1H), 6.15 (d, J = 8.2Hz, 1H), 6.
22 (d, J = 3.3 Hz, 1 H), 6.30 (m, 1
H), 6.73 (d, J = 8.3 Hz, 1H), 7.1
7-7.41 (m, 5H) Example 70 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (3-toluoyl alcohol
Mino) valerylamino] -2-heptanone (Table 1
Production of compound number 141) Melting point: 123-126 ° C IR (KBr, cm^-1): 3285, 1732, 163
5 NMR (CDCl₃, Δ): 0.82 (t, J = 6.8)
Hz, 3H), 0.98 (d, J = 5.9Hz, 6
H), 1.15 to 1.38 (m, 4H), 1.56
(M, 1H), 1.62 to 1.99 (m, 4H), 2.
39 (s, 3H), 3.27 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.65-4.81 (m, 2H), 6.
22 (d, J = 3.0 Hz, 1 H), 6.30 (m, 1
H), 6.56 (d, J = 8.3 Hz, 1H), 6.7
7 (d, J = 7.7 Hz, 1H), 7.28 to 7.34
(M, 2H), 7.36 (m, 1H), 7.55-7.
62 (m, 2H) Example 71 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (4-toluoyl alcohol
Mino) valerylamino] -2-heptanone (Table 1
Production of compound number 142) Melting point: 122-123 ° C IR (KBr, cm^-1): 3292, 1732, 165
7 NMR (CDCl₃, Δ): 0.81 (t, J = 6.7)
Hz, 3H), 0.97 (d, J = 5.6Hz, 6
H), 1.17 to 1.37 (m, 4H), 1.43 to
1.98 (m, 5H), 2.39 (s, 3H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.65
4.81 (m, 2H), 6.22 (d, J = 3.2H
z, 1H), 6.30 (m, 1H), 6.52 (d, J
= 8.0 Hz, 1H), 6.75 (d, J = 7.6H)
z, 1H), 7.24 (d, J = 8.1Hz, 2H),
7.36 (m, 1H), 7.67 (d, J = 8.1H
z, 2H) Example 72 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-trifluoro
Methylbenzoylamino) valerylamino] -2-hep
Production of Tanone (Compound No. 143 of Table-1) Melting point: 102-106 ° C IR (KBr, cm^-1): 3283, 1734, 164
1,1604 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.98 (d, J = 5.8Hz, 6
H), 1.18 to 1.39 (m, 4H), 1.43 to
2.0 (m, 5H), 3.27 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.72
(S, 2H), 4.62-4.81 (m, 2H), 6.
21 (d, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 6.51 (d, J = 8.4 Hz, 1H), 6.8
9 (d, J = 7.6 Hz, 1H), 7.35 (m, 1
H), 7.43 to 7.62 (m, 3H), 7.69 (d
d, J = 9.0Hz, 2.4Hz, 1H) Example 73 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (4-trifluoro
Methylbenzoylamino) valerylamino] -2-hep
Production of Tanone (Compound No. 145 of Table-1) Melting point: 121 to 123 ° C IR (KBr, cm^-1): 3289, 1732, 165
7,1639 NMR (CDCl₃, Δ): 0.83 (t, J = 6.8)
Hz, 3H), 0.97 (d, J = 6.0 Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.43 to
1.82 (m, 4H), 1.87 (m, 1H), 3.2
8 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.74 (s, 2H), 4.63 ~
4.84 (m, 2H), 6.22 (d, J = 3.1H
z, 1H), 6.30 (m, 1H), 6.61 (d, J
= 7.3 Hz, 1H), 6.75 (d, J = 7.9H)
z, 1H), 7.36 (m, 1H), 7.69 (d, J
= 8.4 Hz, 2H), 7.89 (d, J = 8.4H
z, 2H) Example 74 (s) -3-[(s) -2-
(2-fluoro-6-trifluoromethylbenzoylurea
Mino) -4-methylvalerylamino] -1-furfuryl
Of thio-2-heptanone (Compound No. 146 of Table-1)
Manufacturing Melting point: 106-107 ° C IR (KBr, cm^-1): 3266, 1720, 164
1 NMR (CDCl₃, Δ): 0.83 (t, J = 6.7)
Hz, 3H), 0.99 (d, J = 5.0Hz, 6
H), 1.15 to 1.39 (m, 4H), 1.47 to
2.02 (m, 5H), 3.27 (d, J = 15Hz,
1H), 3.35 (d, J = 15 Hz, 1H), 3.7
3 (s, 2H), 4.60 to 4.80 (m, 2H),
6.22 (d, J = 3.1 Hz, 1H), 6.30
(M, 1H), 6.60 (d, J = 7.7Hz, 1
H), 7.13 (dd, J = 8.0 Hz, 7.7 Hz,
1H), 7.20 to 7.36 (m, 1H), 7.37
(M, 1H), 7.75 (m, 1H), 8.38 (d
d, J = 6.7 Hz, 1.9 Hz, 1H) Example 75 (s) -3-[(s) -2-
(2-fluoro-4-trifluoromethylbenzoylurea
Mino) -4-methylvalerylamino] -1-furfuryl
Of thio-2-heptanone (Compound No. 148 of Table-1)
Manufacturing Melting point: 102-106 ° C IR (KBr, cm^-1): 3289, 1732, 164
Three NMR (CDCl₃, Δ): 0.83 (t, J = 6.8)
Hz, 3H), 0.97 (d, J = 6.0 Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.45
2.0 (m, 5H), 3.28 (d, J = 15Hz, 1
H), 3.36 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.63 to 4.84 (m, 2H), 6.
22 (m, 1H), 6.30 (m, 1H), 6.71
(D, J = 7.7 Hz, 1H), 7.13 (dd, J =
11 Hz, 8.0 Hz, 1H), 7.36 (m, 1
H), 7.42 (d, J = 11 Hz, 1H), 7.53
(Dd, J = 8.0 Hz, 0.8 Hz, 1 H), 8.1
8 (dd, J = 7.9Hz, 7.6Hz, 1H) Example 76 (s) -3-[(s) -2-
(4-fluoro-3-trifluoromethylbenzoylurea
Mino) -4-methylvalerylamino] -1-furfuryl
Of thio-2-heptanone (Compound No. 149 of Table-1)
Manufacturing Melting point: 112-114 ° C IR (KBr, cm^-1): 3297, 1715, 164
Two NMR (CDCl₃, Δ): 0.82 (t, J = 6.7)
Hz, 3H), 0.98 (d, J = 5.2Hz, 6
H), 1.15 to 1.40 (m, 4H), 1.45
1.81 (m, 4H), 1.87 (m, 1H), 3.2
8 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.74 (s, 2H), 4.62 ~
4.83 (m, 2H), 6.22 (d, J = 3.3H
z, 1H), 6.30 (m, 1H), 6.64 (d, J
= 7.1 Hz, 1H), 6.93 (d, J = 6.5H)
z, 1H), 7.27 (m, 1H), 7.36 (m, 1
H), 7.99 (m, 1H), 8.05 (dd, J =
6.7Hz, 4.8Hz, 1H) Example 77 (s) -1-furfurylthio
-3-[(s) -2- (2-methoxybenzoylami)
No) -4-methylvalerylamino] -2-heptanone
Production of (Compound No. 151 of Table-1) Melting point: 77 to 78 ° C IR (KBr, cm^-1): 3306, 2953, 173
2,1660,1630,1601 NMR (CDCl₃, Δ): 0.77 (t, J = 6.8)
Hz, 3H), 0.96 (d, J = 6.1Hz, 3
H), 0.98 (d, J = 6.1 Hz, 3H), 1.1
7 to 1.37 (m, 4H), 1.45 to 1.99 (m,
5H), 3.27 (d, J = 15Hz, 1H), 3.3
5 (d, J = 15 Hz, 1 H), 3.72 (s, 2
H), 3.97 (s, 3H), 4.65 to 4.78.
(M, 2H), 6.22 (d, J = 3.2Hz, 1
H), 6.29 (m, 1H), 6.95 to 7.04.
(M, 2H), 7.09 (d, J = 7.3 Hz, 0.5
H), 7.13 (d, J = 7.3 Hz, 0.5 H),
7.35 (m, 1H), 7.46 (d, J = 7.3H
z, 0.5H), 7.50 (d, J = 7.3Hz, 0.
5H), 8.17 (dd, J = 7.8Hz, 1.9H)
z, 2H) Example 78 (s) -1-furfurylthio
-3-[(s) -2- (3-methoxyphenoxyacetyl)
Lumino) -4-methylvalerylamino] -2-hepta
Production of Non (Compound No. 103 in Table-1) IR (neat, cm^-1): 3288, 1730, 16
51,1602 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.93 (d, J = 5.9Hz, 6
H), 1.17 to 1.40 (m, 4H), 1.47 to
1.80 (m, 4H), 1.83 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 3.79
(S, 3H), 4.47 (d, J = 10Hz, 1H),
4.52 (d, J = 10 Hz, 1H), 4.63 (m,
1H), 4.78 (m, 1H), 6.22 (d, J =
3.2 Hz, 1H), 6.29 (m, 1H), 6.50
˜6.65 (m, 3H), 7.01 (t, J = 8.7H
z, 2H), 7.20 (t, J = 8.7Hz, 1H),
7.35 (m, 1H) Example 79 (s) -1-furfurylthio
-3-[(s) -2- (4-methoxybenzoylami)
No) -4-methylvalerylamino] -2-heptanone
Production of (Compound No. 153 of Table-1) Melting point: 124 ° C IR (KBr, cm^-1): 3291, 1732, 165
5,1624 NMR (CDCl₃, Δ): 0.81 (t, J = 6.1)
Hz, 3H), 0.98 (d, J = 5.0Hz, 6
H), 1.15 to 1.35 (m, 4H), 1.45
1.95 (m, 5H), 3.27 (d, J = 15Hz,
1H), 3.36 (d, J = 15Hz, 1H), 3.7
3 (s, 2H), 3.85 (s, 3H), 4.63 ~
4.80 (m, 2H), 6.23 (m, 1H), 6.3
0 (m, 1H), 6.46 (d, J = 8.7 Hz, 1
H), 6.75 (d, J = 7.5 Hz, 1H), 6.9
2 (d, J = 8.8 Hz, 2H), 7.36 (m, 1
H), 7.75 (d, J = 8.8Hz, 2H) Example 80 (s) -3-[(s) -2-
(3,5-dimethoxybenzoylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 155 in Table-1) IR (KBr, cm^-1): 3279, 1713, 163
6 NMR (CDCl₃, Δ): 0.82 (t, J = 6.8)
Hz, 3H), 0.97 (d, J = 5.7Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.45
1.81 (m, 4H), 1.89 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 3.82
(S, 6H), 4.62-4.82 (m, 2H), 6.
22 (d, J = 3.2 Hz, 1H), 6.30 (m, 1
H), 6.55 (d, J = 6.8 Hz, 1H), 6.5
7 (m, 1H), 6.73 (d, J = 6.9 Hz, 1
H), 6.89 (m, 2H), 7.35 (m, 1H) Example 81 (s) -1-furfurylthio
-3-[(s) -2- (4-methoxycarbonylbenzo
Ilamino) -4-methylvalerylamino] -2-hep
Production of Tanone (Compound No. 157 of Table-1) Melting point: 100 to 102 ° C IR (KBr, cm^-1): 3279, 1726, 166
2,1637 NMR (CDCl₃, Δ): 0.82 (t, J = 6.7)
Hz, 3H), 0.98 (d, J = 5.8Hz, 6
H), 1.18 to 1.40 (m, 4H), 1.50
1.64 (m, 1H), 1.64 to 2.0 (m, 4
H), 3.27 (d, J = 15 Hz, 1H), 3.36
(D, J = 15 Hz, 1H), 3.74 (s, 2H),
3.95 (s, 3H), 4.67 to 4.83 (m, 2
H), 6.22 (d, J = 3.2 Hz, 1H), 6.3
0 (m, 1H), 6.75 (d, J = 7.7 Hz, 1
H), 6.81 (d, J = 8.3 Hz, 1H), 7.3
6 (m, 1H), 7.84 (d, J = 8.3 Hz, 2
H), 8.09 (d, J = 8.3 Hz, 2H) Example 82 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (2-naphthoylua
Mino) valerylamino] -2-heptanone (Table 1
Production of compound number 162) Melting point: 97-99 ° C IR (KBr, cm^-1): 3270, 1700, 165
0,1620 NMR (CDCl₃, Δ): 0.77 (t, J = 6.8)
Hz, 3H), 1.0 (d, J = 4.8Hz, 6H),
1.15 to 2.0 (m, 9H), 3.23 to 3.40
(M, 2H), 3.66 (s, 0.7H), 3.73
(S, 1.3H), 4.70-4.96 (m, 2H),
6.21 (d, J = 3.0 Hz, 1H), 6.29
(M, 1H), 6.87 to 7.17 (m, 2H), 7.
21 to 7.40 (m, 1H), 7.47 to 7.63
(M, 2H), 7.76 to 8.0 (m, 4H), 8.2
9 (s, 1H) Example 83 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (1-naphthoylua
Mino) valerylamino] -2-heptanone (Table 1
Production of compound number 161) Melting point: 81-83 ° C IR (KBr, cm^-1): 3270, 1720, 165
0,1630 NMR (CDCl₃, Δ): 0.87 to 0.95 (m,
3H), 1.01 (d, J = 6.3 Hz, 3H), 1.
04 (d, J = 6.3 Hz, 3H), 1.17 to 2.0
(M, 9H), 3.25 to 3.39 (m, 2H), 3.
71 (s, 0.7H), 3.74 (s, 1.3H),
4.75-4.93 (m, 2H), 6.19 (d, J =
3.3 Hz, 0.4 H), 6.23 (d, J = 3.3 H)
z, 0.6H), 6.27 to 6.31 (m, 1H),
6.44 (d, J = 8Hz, 1H), 6.85 (d, J
= 7 Hz, 0.6 H), 6.98 (d, J = 7 Hz,
0.4H), 7.30 to 7.40 (m, 1H), 7.4
1 to 7.70 (m, 4H), 7.92 to 8.0 (m, 2)
H), 8.27-8.39 (m, 1H) Example 84 (s) -1-furfurylthio
-3-[(s) -2- (4-methoxycinnamoylami)
No) -4-methylvalerylamino] -2-heptanone
Production of (Compound No. 165 of Table-1) IR (KBr, cm^-1): 3269, 1715, 164
7,1603 NMR (CDCl₃, Δ): 0.81 (t, J = 6.7)
Hz, 3H), 0.95 (d, J = 4.6Hz, 6
H), 1.17 to 1.38 (m, 4H), 1.46 to
1.79 (m, 4H), 1.87 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 3.80
(S, 3H), 4.67 to 4.84 (m, 2H), 6.
21 (d, J = 3.1 Hz, 1 H), 6.28 (m, 1
H), 6.36 (d, J = 16Hz, 1H), 6.69
(D, J = 8.4 Hz, 1H), 6.83 (d, J =
8.7 Hz, 2 H), 7.26 (d, J = 6.9 Hz,
1H), 7.35 (m, 1H), 7.41 (d, J =
8.7 Hz, 2 H, 7.57 (d, J = 16 Hz, 1
H) Example 85 (s) -3-[(s) -2-
(2,4-dimethoxycinnamoylamino) -3-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 166 of Table-1) IR (KBr, cm^-1): 3270, 1718, 164
5,1604 NMR (CDCl₃, Δ): 0.86 (t, J = 8.6)
Hz, 3H), 0.96 (d, J = 5.6Hz, 6
H), 1.17 to 1.38 (m, 4H), 1.45
1.79 (m, 4H), 1.84 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5 Hz, 1H), 3.73 (s, 2H), 3.83
(S, 3H), 3.84 (s, 3H), 4.63-4.
82 (m, 2H), 6.18 (d, J = 6.8Hz, 1
H), 6.22 (d, J = 3.0 Hz, 1H), 6.2
9 (m, 1H), 6.40 to 6.58 (m, 3H),
7.01 (d, J = 6.4 Hz, 1 H), 7.31
7.42 (m, 2H), 7.79 (d, J = 16Hz,
1H) Example 86 (s) -3-[(s) -2-
(1-Acetyl-4-piperidylcarbonylamino)-
4-Methylvalerylamino] -1-furfurylthio-2
-Production of heptanone (Compound No. 168 of Table-1) Melting point: 110-112 ° C IR (KBr, cm^-1): 3300, 1715, 164
0 NMR (CDCl₃, Δ): 0.81 to 1.01 (m,
9H), 1.19 to 1.39 (m, 4H), 1.47 to
1.78 (m, 6H), 1.78 to 1.97 (m, 3
H), 2.09 (s, 3H), 2.42 (m, 1H),
2.67 (m, 1H), 3.09 (m, 1H), 3.2
9 (d, J = 15 Hz, 1H), 3.34 (d, J = 1
5Hz, 1H), 3.72 (s, 2H), 3.86
(D, J = 13 Hz, 1H), 4.45 to 4.62
(M, 2H), 4.68 (m, 1H), 6.22 (d,
J = 3.0 Hz, 1H), 6.29 (m, 1H), 6.
71 (d, J = 6.2 Hz, 1H), 7.20 (d, J
= 7.4 Hz, 1H), 7.35 (m, 1H) Example 87 (s) -3-[(s) -2-
(1-tert-butoxycarbonyl-4-piperidyl
Carbonylamino) -4-methylvalerylamino] -1
-Furfurylthio-2-heptanone (compound number in Table-1
No. 171) IR (KBr, cm^-1): 3289, 1698, 164
0 NMR (CDCl₃, Δ): 0.78 to 1.02 (m,
9H), 1.13 to 1.71 (m, 10H), 1.45
(S, 9H), 1.71-1.97 (m, 3H), 2.
30 (m, 1H), 2.61 to 2.83 (m, 2H),
3.28 (d, J = 15 Hz, 1H), 3.33 (d,
J = 15 Hz, 1H), 3.72 (s, 2H), 4.0
-4.22 (m, 2H), 4.52 (m, 1H), 4.
69 (m, 1H), 6.22 (m, 1H), 6.29
(M, 1H), 6.43 (d, J = 8.3 Hz, 1
H), 7.05 (d, J = 7.6 Hz, 1H), 7.3
5 (m, 1H) Example 88 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (4-piperidylca)
Rubonylamino) valerylamino] -2-heptanone
Preparation of Hydrochloride (Compound No. 172 of Table-1) IR (KBr, cm^-1): 3350, 3250, 170
0,1660,1635 NMR (CD₃OD, δ: 0.81 to 1.05 (m,
9H), 1.21 to 1.43 (m, 4H), 1.50
1.78 (m, 5H), 1.78 to 2.17 (m, 4)
H), 2.64 (m, 1H), 2.95 to 3.17.
(M, 2H), 3.24 to 3.57 (m, 4H), 3.
72 (s, 2H), 4.39 (dd, J = 7.0 Hz,
7.0Hz, 1H), 4.55 (dd, J = 9.4H
z, 4.3 Hz, 1H), 6.22 (d, J = 2.7H)
z, 1H), 6.32 (m, 1H), 7.41 (m, 1)
H) Example 89 (s) -1-furfurylthio
-3-((s) -4-methyl-2-nicotinoylamino
Valerylamino) -2-heptanone (Compound number in Table-1
No.176) IR (neat, cm^-1): 3280, 1715, 16
60,1630 NMR (CDCl₃, Δ): 0.80 (t, J = 7.0)
Hz, 3H), 0.94 (d, J = 6.7Hz, 6
H), 1.12 to 1.39 (m, 4H), 1.51
(M, 1H), 1.67 to 1.80 (m, 3H), 1.
84 (m, 1H), 3.29 (d, J = 15Hz, 1
H), 3.35 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.70 to 4.84 (m, 2H), 6.
22 (d, J = 3.2 Hz, 1H), 6.30 (m, 1
H), 6.98 (d, J = 7.7 Hz, 1H), 7.1
7 (d, J = 8.0 Hz, 1H), 7.30 to 7.42
(M, 2H), 8.11 (dd, J = 8.0 Hz, 1.
9 Hz, 1 H), 8.73 (dd, J = 4.8 Hz,
1.6 Hz, 1 H), 9.04 (d, J = 1.9 Hz,
1H) Example 90 (s) -3-((s) -2-
Isonicotinoylamino-4-methylvalerylamino)
-1-furfurylthio-2-heptanone (compounds in Table-1
Product No. 177) IR (neat, cm^-1): 3280, 1715, 16
Thirty NMR (CDCl₃, Δ): 0.81 (t, J = 6.7)
Hz, 3H), 0.92 (d, J = 4.0Hz, 6
H), 1.15 to 1.39 (m, 5H), 1.59
(M, 1H), 1.64-1,98 (m, 3H), 3.
33 (s, 2H), 3.73 (s, 2H), 4.68-
4.95 (m, 2H), 6.22 (d, J = 3.2H
z, 1H), 6.30 (m, 1H), 7.35 (d, J
= 1.9 Hz, 1H), 7.43 (d, J = 6.7H)
z, 1H), 7.58 to 7.71 (m, 2H), 7.8.
1 (d, J = 7.5 Hz, 1H), 8.65 to 8.69
(M, 2H) Example 91 (s) -3-[(s) -2-
(2-Benzofuranylcarbonylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 180 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
40 NMR (CDCl₃, Δ): 0.81 (t, J = 6.9)
Hz, 2.2H), 0.89 (t, J = 6.9Hz,
0.8H), 1.0 (d, J = 6.5Hz, 6H),
1.10 to 1.99 (m, 9H), 3.23 to 3.40
(M, 2H), 3.70 (d, J = 5.4Hz, 0.5
H), 3.73 (s, 1.5H), 4.76 to 4.93.
(M, 2H), 6,18 (m, 1H), 6,30 (m,
1H), 6.70 (d, J = 7Hz, 0.75H),
6.76 (d, J = 7 Hz, 0.25H), 7.05
(D, J = 8 Hz, 1 H), 7.25 to 7.59 (m,
5H), 7.67 (d, J = 7.4Hz, 1H) Example 92 (s) -3-[(s) -2-
(3-benzofuranylcarbonylamino) -4-methyl
Valerylamino] -1-furfurylthio-2-heptano
(Compound No. 181 of Table-1) Melting point: 113-116 ° C IR (KBr, cm^-1): 3300, 1710, 163
0 NMR (CDCl₃, Δ): 0.77 (t, J = 6.7)
Hz, 3H), 0.83 to 1.02 (m, 6H), 1.
07-1.38 (m, 5H), 1.41-1.63
(M, 1H), 1.63 to 1.97 (m, 3H), 3.
30 (d, J = 15 Hz, 1 H), 3.35 (d, J =
15Hz, 1H), 3.72 (s, 2H), 4.70
(M, 1H), 4.80 (dt, J = 7.1 Hz, 7.
0Hz, 1H), 6.21 (d, J = 3.1Hz, 1
H), 6.28 (m, 1H), 7.21 to 7.38.
(M, 4H), 7.38 to 7.57 (m, 2H), 7.
93 (m, 1H), 8.23 (d, J = 1.4Hz, 1
H) Example 93 (s) -3-[(s) -2-
(7-fluoro-2-benzofuranylcarbonylami
No) -4-methylvalerylamino] -1-furfurylchi
Preparation of o-2-heptanone (Compound No. 182 of Table-1)
Construction Melting point: 102-103 ° C IR (KBr, cm^-1): 3270, 1700, 165
0 NMR (CDCl₃, Δ): 0.79 (t, J = 6.8)
Hz, 3H), 0.98 (d, J = 4.9Hz, 6
H), 1.18 to 1.40 (m, 4H), 1.60
(M, 1H), 1.64 to 1.97 (m, 4H), 3.
32 (d, J = 15 Hz, 1H), 3.40 (d, J =
15Hz, 1H), 3.75 (s, 2H), 4.75 ~
4.95 (m, 2H), 6.23 (d, J = 3.1H
z, 1H), 6.29 (m, 1H), 7.08 to 7.3.
5 (m, 5H), 7.37 (s, 1H), 7.42 (d
d, J = 7.5Hz, 1.1Hz, 1H) Example 94 (s) -1-furfurylthio
-3-[(s) -4-methyl-2- (4-oxo-4H
-1-Benzopyran-4-ylcarbonylamino) vale
Rylamino] -2-heptanone (Compound No. 1 in Table 1
88) Manufacturing Melting point: 114-115 ° C IR (KBr, cm^-1): 3350, 3250, 170
5,1660,1625 NMR (CDCl₃, Δ): 0.84 (t, J = 6.8)
Hz, 3H), 1.0 (d, J = 9.2Hz, 6H),
1.15 to 2.0 (m, 9H), 3.30 (d, J = 1
5Hz, 1H), 3.38 (d, J = 15Hz, 1
H), 3.75 (s, 2H), 4.69 (m, 1H),
4.82 (m, 1H), 6.23 (d, J = 2.9H
z, 1H), 6.31 (m, 1H), 6.61 (d, J
= 8 Hz, 1H), 7.16 (s, 1H), 7.36-
7.55 (m, 3H), 7.57 (d, J = 14Hz,
1H), 7.72 to 7.80 (m, 1H), 8.22
(Dd, J = 1.6Hz, 7.9Hz, 1H) Example 95 (s) -3-((2s, 3
s) -2-Benzyloxycarbonylamino-3-methyl
Valerylamino) -1-furfurylthio-2-heptano
(Compound No. 205 in Table-1) Melting point: 101 to 103 ° C IR (KBr, cm^-1): 3300, 3250, 170
5,1680,1640 NMR (CDCl₃, Δ): 0.83 to 1.10 (m,
9H), 1.07 to 1.39 (m, 3H), 1.42
1.78 (m, 4H), 1.82 to 2.01 (m, 2)
H), 3.26 (d, J = 15 Hz, 1H), 3.34.
(D, J = 15 Hz, 1H), 3.71 (s, 2H),
4.05 (dt, J = 8.0 Hz, 6.4 Hz, 1
H), 4.80 (m, 1H), 5.12 (s, 2H),
5.30 (d, J = 7.7 Hz, 1H), 6.22
(D, J = 3.3 Hz, 1 H), 6.30 (m, 1
H), 6.43 (d, J = 8.0 Hz, 1H), 7.3
0-7.41 (m, 6H) Example 96 (s) -3-((s) -2-
Benzyloxycarbonylaminohexanoylamino)-
1-furfurylthio-2-heptanone (Compounds of Table-1
No. 206) manufacturing Melting point: 95-97 ° C IR (KBr, cm^-1): 3280, 1730, 169
0,1650 NMR (CDCl₃, Δ): 0.82-0.99 (m,
6H), 1.12 to 1.45 (m, 8H), 1.49 to
1.65 (m, 2H), 1.75 to 1.99 (m, 2
H), 3.27 (d, J = 15 Hz, 1H), 3.34.
(D, J = 15 Hz, 1H), 3.71 (s, 2H),
4.16 (td, J = 7.3 Hz, 6.4 Hz, 1
H), 4.76 (m, 1H), 5.12 (s, 2H),
5.26 (d, J = 7.9 Hz, 1H), 6.21
(D, J = 3.1 Hz, 1 H), 6.29 (m, 1
H), 6.56 (d, J = 6.4 Hz, 1H), 7.2
9 to 7.39 (m, 6H) Example 97 (s) -3-((s) -2-
Benzyloxycarbonylamino-3-phenylpropio
Nylamino) -1-furfurylthio-2-heptanone
Production of (Compound No. 208 of Table-1) Melting point: 123-124 ° C IR (KBr, cm^-1): 3300, 1720, 171
0, 1680, 1640 NMR (CDCl₃, Δ): 0.85 (t, J = 6.9)
Hz, 3H), 1.0 to 1.38 (m, 2H), 1.5
1 (m, 1H), 1.61 to 1.69 (m, 2H),
1.83 (m, 1H), 3.03 (dd, J = 14H
z, 7.0 Hz, 1H), 3.15 (dd, J = 14H
z, 7.0 Hz, 1H), 3.15 (d, J = 15H
z, 1H), 3.22 (d, J = 15Hz, 1H),
3.67 (s, 2H), 4.45 (td, J = 6.9H
z, 6.9 Hz, 1H), 4.70 (m, 1H), 5.
09 (s, 2H), 5.27 (d, J = 5.6Hz, 1
H), 6.21 (d, J = 3.0 Hz, 1H), 6.2
9 (m, 1H), 6.40 (d, J = 6.9 Hz, 1
H), 7.09 to 7.21 (m, 2H), 7.21 to
7.42 (m, 9H) Example 98 (s) -3-((s) -2-
Benzyloxycarbonylamino-3-tert-butoxy
Cypropionylamino) -1-furfurylthio-2-he
Production of Ptanone (Compound No. 210 in Table-1) Melting point: 71-73 ° C IR (KBr, cm^-1): 3300, 1720, 169
0,1660,1640 NMR (CDCl₃, Δ): 0.88 (t, J = 6.8)
Hz, 3H), 1.16 (s, 9H), 1.24 to 1.
41 (m, 4H), 1.59 (m, 1H), 1.91
(M, 1H), 3.24 (d, J = 15Hz, 1H),
3.30 (d, J = 15 Hz, 1H), 3.42 (d
d, J = 7.2 Hz, 7.2 Hz, 1H), 3.71
(S, 2H), 3.84 (m, 1H), 4.26 (m,
1H), 4.77 (m, 1H), 5.10 (d, J = 1
2Hz, 1H), 5.16 (d, J = 12Hz, 1
H), 5.71 (d, J = 5.1 Hz, 1H), 6.2
1 (d, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 7.23 (d, J = 5.1 Hz, 1H), 7.3
5 to 7.41 (m, 6H) Example 99 (s) -3-((s) -2-
Benzyloxycarbonylamino-3-tert-butoxy
Cycarbonylpropionylamino) -1-furfurylchi
Preparation of o-2-heptanone (Compound No. 213 of Table-1)
Construction Melting point: 77 to 78 ° C IR (KBr, cm^-1): 3300, 1720, 169
0,1650 NMR (CDCl₃, Δ): 0.88 (t, J = 6.8)
Hz, 3H), 1.18 to 1.38 (m, 4H), 1.
43 (s, 9H), 1.58 (m, 1H), 1.84
(M, 1H), 2.62 (dd, J = 17Hz, 6.5
Hz, 1H), 2.96 (dd, J = 17Hz, 4.1
Hz, 1H), 3.24 (d, J = 15Hz, 1H),
3.32 (d, J = 15 Hz, 1 H), 3.71 (s,
2H), 4.54 (m, 1H), 4.72 (m, 1)
H), 5.15 (s, 2H), 5.98 (d, J = 8.
5Hz, 1H), 6.22 (d, J = 2.3Hz, 1
H), 6.30 (m, 1H), 7.10 (d, J = 7.
0Hz, 1H), 7.30 to 7.43 (m, 6H) Example 100 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-tert-but
Xycarbonylbutyrylamino) -1-furfurylthio
Preparation of 2-heptanone (Compound No. 216 of Table-1) Melting point: 78 to 79 ° C IR (KBr, cm^-1): 3300, 1730, 171
0,1690,1650 NMR (CDCl₃, Δ): 0.88 (t, J = 6.8)
Hz, 3H), 1.18 to 1.39 (m, 4H), 1.
44 (s, 9H), 1.50 to 1.70 (m, 1H),
1.81-2.17 (m, 3H), 2.31-2.49
(M, 2H), 3.26 (d, J = 15Hz, 1H),
3.29 (d, J = 15 Hz, 1 H), 3.72 (s,
2H), 4.25 (dt, J = 7.4Hz, 6.8H)
z, 1H), 4.75 (m, 1H), 5.11 (s, 2)
H), 5.73 (d, J = 6.8 Hz, 1H), 6.2
2 (d, J = 3.0 Hz, 1 H), 6.29 (m, 1
H), 6.82 (d, J = 7.4 Hz, 1H), 7.2
7 to 7.39 (m, 6H) Example 101 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-carboxybutyi
Rylamino) -1-furfurylthio-2-heptanone
Production of (Compound No. 217 of Table-1) Melting point: 67-71 ° C IR (KBr, cm^-1): 3300, 1720, 170
5,1680,1650 NMR (CDCl₃, Δ): 0.81 to 0.98 (m,
3H), 1.18 to 1.43 (m, 4H), 1.60
(M, 1H), 1.72-2.0 (m, 2H), 2.1
0 (m, 1H), 2.37 (t, J = 7.5 Hz, 2
H), 3.23 to 3.37 (m, 2H), 3.72.
(S, 2H), 4.15 (dt, J = 5.0 Hz, 3.
9Hz, 1H), 4.57 (m, 1H), 5.08
(S, 2H), 6.22 (d, J = 2.9Hz, 1
H), 6.31 (m, 1H), 7.21 to 7.39.
(M, 5H), 7.40 (m, 1H) Example 102 (s) -3-((s) -2
-Benzyloxycarbonylamino-6-tert-but
Xycarbonylaminohexanoylamino) -1-full
Furylthio-2-heptanone (Compound No. 22 in Table-1
0) Manufacturing Melting point: 60 to 63 ° C IR (KBr, cm^-1): 3350, 1725, 169
0,1650 NMR (CDCl₃, Δ): 0.87 (t, J = 6.7)
Hz, 3H), 1.15 to 1.78 (m, 10H),
1.41 (s, 9H), 1.79 to 1.99 (m, 2
H), 2.97 to 3.18 (m, 2H), 3.25.
(D, J = 15 Hz, 1H), 3.35 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 4.18 (m,
1H), 4.59 to 4.82 (m, 2H), 5.10
(S, 2H), 5.63 (m, 1H), 6.22 (d,
J = 2.9 Hz, 1H), 6.29 (m, 1H), 6.
78 (d, J = 7.8 Hz, 1H), 7.24 to 7.4
1 (m, 6H) Example 103 (s) -3-((s) -6
-Amino-2-benzyloxycarbonylaminoheptano
Ilamino) -1-furfurylthio-2-heptanone
Production of Hydrochloride (Compound No. 221 of Table-1) Melting point: 95 ° C (decomposition) IR (KBr, cm^-1): 3310, 1720, 168
0,1635 NMR (CDCl₃, Δ): 0.85 to 1.05 (m,
3H), 1.22 to 1.42 (m, 4H), 1.42
2.0 (m, 8H), 2.96 (t, J = 7.5 Hz,
2H), 3.44 (s, 2H), 3.76 (s, 2)
H), 4.18 (dd, J = 8.5 Hz, 5.8 Hz,
1H), 4.64 (m, 1H), 5.14 (s, 2)
H), 6.27 (d, J = 3.1 Hz, 1H), 6.3
7 (m, 1H), 7.26 to 7.43 (m, 5H),
7.46 (m, 1H), 8.33 (d, J = 7.9H
z, 1H) Example 104 (s) -3-((s) -2
-Benzyloxycarbonylamino-2-phenylacetyl
Ruamino) -1-furfurylthio-2-heptanone (Table
-1 Compound No. 224) Melting point: 144-146 ° C IR (KBr, cm^-1): 3300, 1710, 164
0 NMR (CDCl₃, Δ): 0.87 (t, J = 7.1)
Hz, 3H), 1.07 to 1.39 (m, 4H), 1.
42-1.63 (m, 1H), 1.81-1.99
(M, 1H), 3.13 (s, 2H), 3.54 (d,
J = 15Hz, 1H), 3.59 (d, J = 15Hz,
1H), 4.71 (m, 1H), 5.03 (d, J = 1
2Hz, 1H), 5.11 (d, J = 12Hz, 1
H), 5.23 (d, J = 6.1 Hz, 1H), 6.0
7 (d, J = 6.3 Hz, 1H), 6.10 (d, J =
3.1 Hz, 1H), 6.21 (m, 1H), 6.31
(D, J = 7.4 Hz, 1H), 7.24 to 7.43
(M, 11H) Example 105 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-pyridylmethylthio) -2-hep
Production of Tanone (Compound No. 226 of Table-1) IR (neat, cm^-1): 3304, 1711, 16
58 NMR (CD₃OD, δ: 0.80 to 1.0 (m, 9)
H), 1.16 to 1.40 (m, 4H), 1.45
1.98 (m, 5H), 3.25 to 3.40 (m, 2
H), 3.80 (s, 2H), 4.15 (m, 1H),
4.57 (m, 1H), 5.07 (s, 2H), 7.2
5 to 7.39 (m, 6H), 7.42 (d, J = 7.8)
Hz, 1H), 7.76 (ddd, J = 7.7Hz,
7.7 Hz, 1.8 Hz, 1H), 8.44 (m, 1
H) Example 106 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (3-pyridylmethylthio) -2-hep
Production of Tanone (Compound No. 228 of Table-1) IR (neat, cm^-1): 3409, 1717, 16
53 NMR (CD₃OD, δ: 0.92 to 1.03 (m,
9H), 1.18 to 1.43 (m, 4H), 1.47 to
1.98 (m, 5H), 3.36 (d, J = 15Hz,
1H), 3.42 (d, J = 15Hz, 1H), 3.9
4 (s, 2H), 4.15 (dd, J = 7.6 Hz,
7.5 Hz, 1H), 4.48 (dd, J = 9.6H)
z, 4.4 Hz, 1H), 5.06 (d, J = 10H
z, 1H), 5.11 (d, J = 10Hz, 1H),
7.21 to 7.40 (m, 5H), 8.04 (dd, J
= 8.0 Hz, 5.8 Hz, 1H), 8.62 (d, J
= 8.0 Hz, 1H), 8.75 (d, J = 5.8H
z, 1H), 8.83 (s, 1H) Example 107 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (4-pyridylmethylthio) -2-hep
Production of Tanone (Compound No. 230 of Table-1) IR (neat, cm^-1): 3300, 1720, 17
05,1660,1600 NMR (CDCl₃, Δ): 0.86 (t, J = 6.7)
Hz, 3H), 0.91 to 0.95 (m, 6H), 1.
13-1.39 (m, 5H), 1.41-1.78
(M, 3H), 1.84 (m, 1H), 3.11 (d,
J = 15Hz, 1H), 3.24 (d, J = 15Hz,
1H), 3.63 (s, 2H), 4.22 (m, 1
H), 4.75 (m, 1H), 5.11 (s, 2H),
5.38 (d, J = 8.0 Hz, 1H), 6.81
(D, J = 6.9 Hz, 1H), 7.15 to 7.31
(M, 2H), 7.31 to 7.41 (m, 5H), 8.
45-8.60 (m, 2H) Example 108 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4-cyclohexyl-1-methylthio-2-
Production of butanone (Compound No. 236 of Table-1) Melting point: 83 to 84 ° C IR (KBr, cm^-1): 3320, 1684, 164
8 NMR (CDCl₃, Δ): 0.90 to 1.05 (m,
8H), 1.05 to 1.88 (m, 14H), 2.06
(S, 3H), 3.20 (d, J = 14Hz, 1H),
3.38 (d, J = 14 Hz, 1H), 4.18 (m,
1H), 4.88 (m, 1H), 5.12 (s, 2
H), 5.13 (m, 1H), 6.43 (d, J = 7H
z, 1H), 7.35 (s, 5H) Example 109 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4-cyclohexyl-1-furfurylthio-
Preparation of 2-butanone (Compound No. 238 of Table-1) IR (neat, cm^-1): 3320, 1700, 16
Fifty NMR (CDCl₃, Δ): 0.78 to 1.0 (m, 8)
H), 1.04 to 1.85 (m, 14H), 3.24.
(D, J = 13 Hz, 1H), 3.35 (d, J = 13
Hz, 1H), 3.71 (s, 2H), 4.10 (m,
1H), 4.78 (m, 1H), 5.07 (m, 1
H), 5.12 (s, 2H), 6.22 (d, J = 3.
2 Hz, 1H), 6.30 (m, 1H), 6.38
(D, J = 8 Hz, 1H), 7.35 (s, 5H),
7.39 (m, 1H) Example 110 (s) -4-cyclohexyl
Ru-1-furfurylthio-3-((s) -4-methyl-
2-phenoxyacetylaminovalerylamino) -2-
Production of butanone (Compound No. 240 of Table-1) IR (neat, cm^-1): 3310, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.88 to 1.07 (m,
8H), 1.07 to 1.88 (m, 14H), 3.28.
(D, J = 15 Hz, 1H), 3.36 (d, J = 15
Hz, 1H), 3.73 (s, 2H), 4.53 (s,
2H), 4.57 (m, 1H), 4.80 (m, 1)
H), 6.21 (d, J = 3.2 Hz, 1H), 6.3
2 (m, 1H), 6.48 (d, J = 8Hz, 1H),
6.87-6.99 (m, 3H), 7.05 (t, J =
8Hz, 1H), 7.30 to 7.40 (m, 3H) Example 111 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-mercapto-4-phenyl-2-butano
(Compound No. 242 of Table-1) Melting point: 171 ° C IR (KBr, cm^-1): 3320, 1720, 169
0,1655 NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 6)
H), 1.30 to 1.70 (m, 3H), 2.92 (d
d, J = 7.6 Hz, 14 Hz, 1H), 3.03 to
3.25 (m, 2H), 3.38 (d, J = 15Hz,
1H), 4.13 (m, 1H), 4.85 (m, 1
H), 4.95-5.18 (m, 2H), 5.25
(M, 1H), 6.76 (d, J = 7Hz, 1H),
7.05 to 7.45 (m, 10H) Example 112 (s) -3-((s) -2
-Tert-butoxycarbonylamino-4-methylva
Relylamino) -1-methylthio-4-phenyl-2-
Production of butanone (Compound No. 243 of Table-1) Melting point: 117-118 ° C IR (KBr, cm^-1): 3360, 1705, 166
0 NMR (CDCl₃, Δ): 0.85 to 1.05 (m,
6H), 1.25 to 1.70 (m, 3H), 1.44
(S, 9H), 1.98 (s, 3H), 2.95-3.
25 (m, 4H), 4.04 (m, 1H), 4.77
(M, 1H), 5.06 (m, 1H), 6.67 (m,
1H), 7.15 to 7.38 (m, 5H) Example 113 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylthio-4-phenyl-2-butano
(Compound No. 244 of Table-1) Melting point: 81-91 ° C IR (KBr, cm^-1): 3340, 3290, 172
0,1683,1652 NMR (CDCl₃, Δ): 0.89 (d, J = 5.8)
Hz, 6H), 1.30 to 1.65 (m, 3H), 1.
99 (s, 3H), 2.90 to 3.25 (m, 4H),
4.10 (m, 1H), 4.95 to 5.15 (m, 2
H), 5.10 (s, 2H), 6.55 (m, 1H),
7.08 to 7.43 (m, 10H) Example 114 (s) -3-[(s) -N
-Methyl-2- (benzyloxycarbonylamino) -4
-Methylvalerylamino] -1-methylthio-4-phen
Production of Nil-2-butanone (Compound No. 245 of Table-1)
Construction IR (neat, cm^-1): 3300, 1720, 16
40 NMR (CDCl₃, Δ): 0.85-1.0 (m, 6
H), 1.20 to 1.82 (m, 3H), 2.0 (s,
3H), 2.84 (s, 3H), 2.97 (d, J = 1)
4Hz, 1H), 3.0 (d, J = 14Hz, 1H),
3.26 (d, J = 14 Hz, 1H), 3.35 (d,
J = 14 Hz, 1H), 4.54 (m, 1H), 4.9
0 (m, 1H), 5.07 (s, 2H), 5.26
(D, J = 8 Hz, 1 H), 7.15 to 7.35 (m,
10H) Example 115 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylsulfinyl-4-phenyl-2
-Production of butanone (Compound No. 248 of Table-1) Melting point: 97-102 ° C IR (KBr, cm^-1): 3320, 1715, 168
5,1648 NMR (CDCl₃, Δ): 0.70 to 0.95 (m,
6H), 1.10 to 1.70 (m, 3H), 2.84
(S, 2.1H), 2.87 (s, 0.9H), 2.8
0 to 3.03 (m, 3H), 3.13 to 3.45 (m,
2H), 3.50 to 3.75 (m, 1H), 4.0
4.20 (m, 1H), 4.28 to 4.88 (m, 2
H), 4.95-5.10 (m, 1H), 5.09
(S, 1.4H), 5.13 (s, 0.6H), 7.1
0-7.55 (m, 10H) Example 116 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylsulfonyl-4-phenyl-2-
Production of butanone (Compound No. 249 of Table-1) Melting point: 142-144 ° C IR (KBr, cm^-1): 3400, 3200, 171
8,1652 NMR (DMSO-d₆, Δ): 0.78 (d, J =
8.4Hz, 3H), 0.82 (d, J = 8.4Hz,
3H), 1.15 to 1.65 (m, 3H), 2.78.
(M, 1H), 3.06 (s, 3H), 3.18 (m,
1H), 3.34 (s, 2H), 3.95 (m, 1
H), 4.40 to 4.60 (m, 2H), 5.01
(S, 2H), 7.13 to 7.58 (m, 10H),
8.50 (d, J = 8Hz, 1H) Example 117 (s) -3-((s) -2
-Amino-4-methylvalerylamino) -1-methylthio
O-4-Phenyl-2-butanone hydrochloride (Compound of Table-1
Production of compound number 250) Melting point: 141 ° C IR (KBr, cm^-1): 3400, 1698, 165
8 NMR (DMSO-d₆, Δ): 0.85 (d, J =
2.4Hz, 3H), 0.87 (d, J = 2.3Hz,
3H), 1.45 to 1.70 (m, 3H), 1.97
(S, 3H), 2.88 (dd, J = 8.8Hz, 14
Hz, 1H), 3.16 (dd, J = 5.1Hz, 14
Hz, 1H), 3.43 (d, J = 15Hz, 1H),
3.53 (d, J = 15 Hz, 1 H), 3.75 (m,
1H), 4.77 (m, 1H), 7.15 to 7.35.
(M, 5H), 8.28 (s, 3H), 9.11 (d,
J = 7.3Hz, 1H) Example 118 (s) -3-((s) -2
-Acetylamino-4-methylvalerylamino) -1-
Methylthio-4-phenyl-2-butanone (Table 1
Production of compound number 251) Melting point: 118-120 ° C IR (KBr, cm^-1): 3320, 1720, 164
5 NMR (CDCl₃, Δ): 0.89 (d, J = 4.0)
Hz, 3H), 0.91 (d, J = 4.1Hz, 3
H), 1.35 to 1.70 (m, 3H), 1.95
(S, 3H), 1.99 (s, 3H), 2.90-3.
25 (m, 4H), 4.40 (m, 1H), 5.06
(Q, J = 6.8 Hz, 1H), 5.83 (d, J = 7
Hz, 1H), 6.77 (d, J = 7Hz, 1H),
7.15 ~ 7.38 (m, 5H) Example 119 (s) -3-[(s) -4
-Methyl-2- (3-phenylpropionylamino) va
Lerylamino] -1-methylthio-4-phenyl-2-
Production of butanone (Compound No. 254 of Table-1) Melting point: 104-107 ° C IR (KBr, cm^-1): 3320, 3275, 171
5,1640 NMR (CDCl₃, Δ): 0.83 (d, J = 3.8)
Hz, 3H), 0.85 (d, J = 3.9Hz, 3
H), 1.25 to 1.65 (m, 3H), 1.99.
(S, 3H), 2.40 to 2.58 (m, 2H), 2.
85-3.22 (m, 6H), 4.37 (m, 1H),
5.07 (q, J = 7.2 Hz, 1H), 5.61
(D, J = 7.6 Hz, 1H), 6.64 (d, J =
7.6 Hz, 1 H), 7.10 to 7.35 (m, 10
H) Example 120 (s) -3-[(s) -4
-Methyl-2- (1-naphthylacetylamino) valeri
Lumino] -1-methylthio-4-phenyl-2-buta
Production of Non (Compound No. 256 of Table-1) Melting point: 126-129 ° C IR (KBr, cm^-1): 3300, 1720, 165
0 NMR (CDCl₃, Δ): 0.55 to 0.68 (m,
6H), 0.98 to 1.45 (m, 3H), 1.99
(S, 3H), 2.84 (m, 1H), 3.0 to 3.2.
0 (m, 3H), 3.90 to 4.10 (m, 2H),
4.30 (m, 1H), 4.94 (m, 1H), 5.3
8 (d, J = 8 Hz, 0.7 H), 5.50 (d, J =
8 Hz, 0.3 H), 6.53 (m, 1 H), 7.03
~ 7.54 (m, 9H), 7.78 to 7.92 (m, 3)
H) Example 121 (s) -3-((s) -4
-Methyl-2- (2-naphthylacetylamino) valeri
Luamino-1-methylthio-4-phenyl-2-butano
(Compound No. 257 of Table-1) Melting point: 112-114 ° C IR (KBr, cm^-1): 3300, 1730, 164
5 NMR (CDCl₃, Δ): 0.73 to 0.83 (m,
6H), 1.20 to 1.60 (m, 3H), 1.97
(S, 0.9H), 1.98 (s, 2.1H), 2.9
6 (m, 1H), 3.04 to 3.20 (m, 3H),
3.62 to 3.75 (m, 2H), 4.37 (m, 1)
H), 5.01 (q, J = 6.7 Hz, 1H), 5.6
2 (d, J = 8Hz, 0.7H), 5.70 (d, J =
8 Hz, 0.3 H), 6.61 (m, 1 H), 7.05
~ 7.19 (m, 2H), 7.22 ~ 7.35 (m, 4
H), 7.40 to 7.56 (m, 2H), 7.63 to
7.72 (m, 1H), 7.75 to 7.90 (m, 3)
H) Example 122 (s) -3-((s) -4
-Methyl-2-phenylsulfonylaminovalerylami
No) -1-methylthio-4-phenyl-2-butanone
Production of (Compound No. 262 of Table-1) Melting point: 133-136 ° C IR (KBr, cm^-1): 3350, 3280, 170
0,1675,1645 NMR (CDCl₃, Δ): 0.50 to 0.90 (m,
6H), 1.20 to 1.60 (m, 3H), 1.97
(S, 1.8H), 1.98 (s, 1.2H), 2.8
0 to 3.20 (m, 4H), 3.63 (m, 1H),
4.90-5.10 (m, 2H), 6.41 (d, J =
7 Hz, 0.4 H), 6.62 (d, J = 7 Hz, 0.
6H), 7.09 to 7.35 (m, 5H), 7.45 to
7.64 (m, 3H), 7.73 to 7.95 (m, 2
H) Example 123 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-octylthio-4-phenyl-2-buta
Production of Non (Compound No. 268 of Table-1) Melting point: 69 ° C IR (KBr, cm^-1): 3340, 3305, 171
5,1690,1650 NMR (CDCl₃, Δ: 0.75 to 1.0 (m, 9)
H), 1.15 to 1.70 (m, 15H), 2.35.
(T, J = 7.2 Hz, 2H), 2.90 to 3.25
(M, 4H), 4.0 to 4.20 (m, 1H), 4.8
8 to 5.20 (m, 2H), 5.08 (s, 2H),
6.56 (m, 1H), 7.07 to 7.45 (m, 10
H) Example 124 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-chloroethylthio) -4-phenyl
Preparation of le-2-butanone (Compound No. 271 of Table-1) Melting point: 77-80 ° C IR (KBr, cm^-1): 3310, 3270, 171
5,1680,1650 NMR (CDCl₃, Δ): 0.83 to 1.0 (m, 6)
H), 1.38 to 1.60 (m, 3H), 2.65
2.85 (m, 2H), 3.0 to 3.30 (m, 4
H), 3.45 to 3.65 (m, 2H), 4.11
(M, 1H), 4.90 to 5.08 (m, 2H), 5.
10 (s, 2H), 6.65 (m, 1H), 7.10
7.35 (m, 10H) Example 125 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-methoxyethylthio) -4-phen
Preparation of Nil-2-butanone (Compound No. 272 of Table-1)
Construction Melting point: 68-69 ° C IR (KBr, cm^-1): 3340, 3300, 172
5,1685,1660 NMR (CDCl₃, Δ): 0.90 (d, J = 5.9)
Hz, 6H), 1.30 to 1.75 (m, 3H), 2.
61 (t, J = 6.2 Hz, 2H), 3.0 (dd, J
= 6.8 Hz, 13 Hz, 1H), 3.16 (dd, J
= 6.8 Hz, 13 Hz, 1 H), 3.26 (d, J =
4.5Hz, 2H), 3.32 (s, 3H), 3.50
(T, J = 6.2 Hz, 2H), 4.12 (m, 1
H), 4.97 (m, 1H), 5.07 (d, J = 7H
z, 1H), 5.10 (s, 2H), 6.59 (d, J
= 7 Hz, 1H), 7.10 to 7.35 (m, 10H) Example 126 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-dimethylaminoethylthio) -4
-Phenyl-2-butanone (Compound No. 27 of Table-1
5) Manufacturing Melting point: 67-69 ° C IR (KBr, cm^-1): 3320, 1710, 165
5 NMR (CDCl₃, Δ): 0.90 to 1.0 (m, 6)
H), 1.20 to 1.75 (m, 3H), 2.28.
(S, 3H), 2.31 (s, 3H), 2.50-2.
75 (m, 4H), 2.98 (m, 1H), 3.08-
3.32 (m, 2H), 3.44 (m, 1H), 4.1
8 (m, 1H), 4.97-5.35 (m, 2H),
5.10 (s, 2H), 6.85 (m, 1H), 7.1
3 to 7.50 (m, 10H) Example 127 (s) -1- (2-acetyl)
Ruaminoethylthio) -3-((s) -2-benzyloxy
Cycarbonylamino-4-methylvalerylamino) -4
-Phenyl-2-butanone (Compound No. 27 of Table-1
6) Manufacturing Melting point: 122-123 ° C IR (KBr, cm^-1): 3320, 1725, 169
0,1642 NMR (CDCl₃, Δ): 0.83 to 0.98 (m,
6H), 1.30 to 1.70 (m, 3H), 1.97
(S, 3H), 2.45 to 2.68 (m, 2H), 2.
90-3.45 (m, 6H), 4.12 (m, 1H),
4.95 to 5.15 (m, 2H), 5.09 (s, 2
H), 6.21 (m, 1H), 6.68 (d, J = 7H
z, 1H), 7.10 to 7.40 (m, 10H) Example 128 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-benzylthio-4-phenyl-2-buta
Production of Non (Compound No. 277 of Table-1) Melting point: 86-87 ° C IR (KBr, cm^-1): 3320, 1700, 168
0,1658 NMR (CDCl₃, Δ): 0.87 (d, J = 6.0)
Hz, 3H), 0.89 (d, J = 6.1Hz, 3
H), 1.35 to 1.70 (m, 3H), 2.88 to
3.22 (m, 4H), 3.69 (s, 2H), 4.1
2 (m, 1H), 4.95 to 5.18 (m, 2H),
5.09 (s, 2H), 6.53 (m, 1H), 7.1
0 to 7.50 (m, 15H) Example 129 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4-phenyl-1-phenylthio-2-buta
Production of Non (Compound No. 279 of Table-1) Melting point: 105 to 106 ° C IR (KBr, cm^-1): 3330, 3280, 171
3,1685,1653 NMR (CDCl₃, Δ): 0.87 (d, J = 6.2)
Hz, 6H), 1.30 to 1.70 (m, 3H), 2.
88-3.18 (m, 2H), 3.63 (s, 2H),
4.13 (m, 1H), 4.95-5.18 (m, 2)
H), 5.09 (s, 2H), 6.53 (m, 1H),
7.05 to 7.15 (m, 2H), 7.15 to 7.50
(M, 13H) Example 130 (s) -3-benzyloxy
Carbonylaminoacetylamino-1-furfurylthio
-4-phenyl-2-butanone (Compound No. 2 in Table-1
80) Manufacturing IR (neat, cm^-1): 3320, 1720, 16
70 NMR (CDCl₃, Δ): 2.95 to 3.20 (m,
2H), 3.16 (s, 2H), 3.63 (s, 2)
H), 3.83 (d, J = 5.7 Hz, 2H), 5.0
6 (q, J = 6.8 Hz, 1H), 5.12 (s, 2
H), 5.30 (m, 1H), 6.18 (m, 1H),
6.29 (m, 1H), 6.53 (d, J = 7Hz, 1
H), 7.07 to 7.50 (m, 11H) Example 131 (s) -3-((s) -2
-Benzyloxycarbonylamino-3-methylbutyryl
Amino) -1-furfurylthio-4-phenyl-2-bu
Production of Tanone (Compound No. 282 of Table-1) Melting point: 122-125 ° C IR (KBr, cm^-1): 3340, 3290, 173
2,1692,1661 NMR (CDCl₃, Δ): 0.81 (d, J = 6.8)
Hz, 3H), 0.90 (d, J = 6.7Hz, 3
H), 2.07 (m, 1H), 2.92 to 3.25.
(M, 4H), 3.62 (s, 2H), 3.96 (m,
1H), 4.98 to 5.28 (m, 2H), 5.11
(S, 2H), 6.18 (d, J = 3.0Hz, 1
H), 6.29 (m, 1H), 6.44 (d, J = 8H
z, 1H), 7.08 to 7.50 (m, 11H) Example 132 (s) -1-furfurylchi
O-3-((s) -2-isobutoxycarbonylamino
-4-Methylvalerylamino) -4-phenyl-2-bu
Production of Tanone (Compound No. 284 of Table-1) Melting point: 89 to 90 ° C IR (KBr, cm^-1): 3340, 3290, 173
0,1690,1655 NMR (CDCl₃, Δ): 0.83 to 0.98 (m,
12H), 1.30 to 1.70 (m, 3H), 1.92
(M, 1H), 2.98 (dd, J = 7.5 Hz, 14
Hz, 1H), 3.08 to 3.25 (m, 3H), 3.
63 (s, 2H), 3.83 (d, J = 6.6Hz, 2
H), 4.13 (m, 1H), 4.88 (m, 1H),
5.02 (d, J = 7.5 Hz, 1H), 6.19
(D, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 6.57 (d, J = 7 Hz, 1H), 7.15
(D, J = 7.7 Hz, 2H), 7.19 to 7.32.
(M, 3H), 7.35 (m, 1H) Example 133 (s) -3-((s) -2
-Tert-butoxycarbonylamino-4-methylva
Relylamino) -1-furfurylthio-4-phenyl-
Preparation of 2-butanone (Compound No. 285 of Table-1) IR (KBr, cm^-1): 3320, 1705, 169
0,1655 NMR (CDCl₃, Δ): 0.89 (d, J = 6.1)
Hz, 3H), 0.91 (d, J = 6.2Hz, 3
H), 1.30 to 1.75 (m, 3H), 1.43
(S, 9H), 3.01 (dd, J = 7.0Hz, 14
Hz, 1H), 3.14 (dd, J = 6.8Hz, 14
Hz, 1H), 3.16 (s, 2H), 3.62 (s,
2H), 4.08 (m, 1H), 4.75 (m, 1
H), 5.02 (m, 1H), 6.18 (d, J = 3.
0 Hz, 1H), 6.29 (m, 1H), 6.65
(D, J = 7 Hz, 1 H), 7.10 to 7.20 (m,
2H), 7.20 to 7.32 (m, 3H), 7.35.
(M, 1H) Example 134 (s) -3-((s) -2
-Cyclopentylmethoxycarbonylamino-3-methyl
Luvalerylamino) -1-furfurylthio-4-phenyl
Preparation of Le-2-butanone (Compound No. 287 of Table-1) Melting point: 77 to 78 ° C IR (KBr, cm^-1): 3340, 3290, 171
5,1692,1660 NMR (CDCl₃, Δ): 0.89 (d, J = 6.0)
Hz, 3H), 0.91 (d, J = 6.1Hz, 3
H), 1.15 to 1.83 (m, 11H), 2.16
(M, 1H), 3.01 (dd, J = 6.5Hz, 14
Hz, 1H), 3.07 to 3.25 (m, 3H), 3.
63 (s, 2H), 3.93 (d, J = 7.1 Hz, 2
H), 4.13 (m, 1H), 4.87 (m, 1H),
5.0 (q, J = 7.3 Hz, 1H), 6.18 (d,
J = 3.2 Hz, 1H), 6.29 (m, 1H), 6.
62 (d, J = 7 Hz, 1 H), 7.14 (d, J =
6.1 Hz, 2H), 7.16 to 7.35 (m, 4H) Example 135 (s) -3-((s) -2
-Cyclohexylmethoxycarbonylamino-3-methyl
Luvalerylamino) -1-furfurylthio-4-phenyl
Preparation of le-2-butanone (Compound No. 288 of Table-1) IR (neat, cm^-1): 3330, 1735, 16
92,1660 NMR (CDCl₃, Δ): 0.80 to 1.05 (m,
8H), 1.10 to 1.80 (m, 12H), 3.01
(Dd, J = 6.8Hz, 14Hz, 1H), 3.07
˜3.25 (m, 3H), 3.63 (s, 2H), 3.
83 (d, J = 7.5 Hz, 2H), 4.09 (m, 1
H), 4.90 (m, 1H), 4.99 (q, J = 7.
5Hz, 1H), 6.21 (d, J = 2.8Hz, 1
H), 6.32 (m, 1H), 6.58 (d, J = 7H
z, 1H), 7.05 to 7.37 (m, 6H) Example 136 (s) -3-((s) -2
-Cycloheptyl methoxycarbonylamino-4-methyl
Luvalerylamino) -1-furfurylthio-4-phenyl
Preparation of le-2-butanone (Compound No. 289 of Table-1) Melting point: 77 to 79 ° C IR (KBr, cm^-1): 3350, 3300, 171
8,1690,1660 NMR (CDCl₃, Δ): 0.89 (d, J = 6.0)
Hz, 3H), 0.91 (d, J = 6.1Hz, 3
H), 1.10 to 1.90 (m, 16H), 2.99.
(Dd, J = 6.7Hz, 15Hz, 1H), 3.08
˜3.25 (m, 3H), 3.63 (s, 2H), 3.
87 (d, J = 5.8 Hz, 2H), 4.12 (m, 1
H), 4.88 (m, 1H), 4.99 (q, J = 6.
7 Hz, 1 H), 6.18 (d, J = 3.1 Hz, 1
H), 6.29 (m, 1H), 6.61 (d, J = 7H
z, 1H), 7.13 (d, J = 7.8Hz, 2H),
7.18-7.38 (m, 4H) Example 137 (s) -3-[(s) -2
-(3-Cyclohexenyl) methoxycarbonylamino
-4-Methylvalerylamino] -1-furfurylthio-
4-phenyl-2-butanone (Compound No. 29 in Table-1
3) Manufacturing Melting point: 85-87 ° C IR (KBr, cm^-1): 3340, 3310, 173
8,1688,1660 NMR (CDCl₃, Δ): 0.90 (d, J = 6.0)
Hz, 3H), 0.91 (d, J = 6.2Hz, 3
H), 1.20-2.20 (m, 10H), 3.01
(Dd, J = 6.8Hz, 14Hz, 1H), 3.08
-3.29 (m, 3H), 3.63 (s, 2H), 3.
96 (d, J = 6.4 Hz, 2H), 4.13 (m, 1
H), 4.92 (m, 1H), 5.03 (q, J = 6.
8Hz, 1H), 5.60-5.76 (m, 2H),
6.19 (d, J = 2.9 Hz, 1H), 6.29
(M, 1H), 6.58 (d, J = 7Hz, 1H),
7.08-7.38 (m, 6H) Example 138 (s) -3-((s) -2
-Cyclohexyloxycarbonylamino-4-methyl
Valerylamino) -1-furfurylthio-4-phenyl
Preparation of 2-butanone (Compound No. 296 of Table-1) Melting point: 102-103 ° C IR (KBr, cm^-1): 3330, 3270, 171
8,1681,1660 NMR (CDCl₃, Δ): 0.89 (d, J = 6.1)
Hz, 3H), 0.91 (d, J = 6.3Hz, 3
H), 1.35 to 1.93 (m, 13H), 3.01
(Dd, J = 6.5Hz, 14Hz, 1H), 3.08
˜3.25 (m, 3H), 3.63 (s, 2H), 4.
12 (m, 1H), 4.62 (m, 1H), 4.84
(M, 1H), 5.01 (q, J = 6.5Hz, 1
H), 6.18 (d, J = 2.9 Hz, 1H), 6.2
9 (m, 1H), 6.66 (d, J = 7Hz, 1H),
7.14 (d, J = 6.1 Hz, 2H), 7.20-
7.35 (m, 4H) Example 139 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-4-phenyl-2-bu
Production of Tanone (Compound No. 297 of Table-1) Melting point: 103-105 ° C IR (KBr, cm^-1): 3350, 3300, 172
5,1690,1658 NMR (CDCl₃, Δ): 0.90 (d, J = 6.2)
Hz, 6H), 1.30 to 1.65 (m, 3H), 2.
96 (dd, J = 7.0 Hz, 14 Hz, 1 H), 3.
07-3.28 (m, 3H), 3.63 (s, 2H),
4.13 (m, 1H), 4.85 to 5.10 (m, 2
H), 5.09 (s, 2H), 6.18 (d, J = 3.
0Hz, 1H), 6.29 (d, J = 3.0Hz, 1
H), 6.56 (d, J = 7 Hz, 1H), 7.05
7.22 (m, 11H) Example 140 (s) -3-((R) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-4-phenyl-2-bu
Production of Tanone (Compound No. 297 of Table-1) Melting point: 77 to 78 ° C IR (KBr, cm^-1): 3300, 1730, 169
0,1650 NMR (CDCl₃, Δ): 0.80 to 0.95 (m,
6H), 1.20 to 1.70 (m, 3H), 3.0
(M, 1H), 3.12 to 3.20 (m, 3H), 3.
63 (d, J = 4.2 Hz, 2H), 4.11 (m, 1
H), 4.95-5.10 (m, 2H), 5.09
(S, 2H), 6.19 (d, J = 2.9Hz, 1
H), 6.28 (m, 1H), 6.50 (m, 1H),
7.07 to 7.40 (m, 11H) Example 141 (s) -1-furfurylchi
O-3-[(s) -N-methyl-2- (benzyloxyca
Rubonylamino) -4-methylvalerylamino] -4-
Phenyl-2-butanone (Compound No. 298 of Table-1)
Manufacturing of IR (neat, cm^-1): 3320, 1720, 16
Fifty NMR (CDCl₃, Δ): 0.85 to 0.98 (m,
6H), 1.20 to 1.75 (m, 3H), 2.80
(S, 3H), 3.02 (m, 1H), 3.08 (d,
J = 15 Hz, 1 H), 3.23 (d, J = 15 Hz,
1H), 3.30 (m, 1H), 3.65 (s, 3
H), 4.50 (m, 1H), 4.74 (m, 1H),
5.06 (s, 2H), 5.20 (d, J = 8.5H
z, 1H), 6.18 (d, J = 3.1Hz, 1H),
6.30 (m, 1H), 7.14 to 7.35 (m, 11
H) Example 142 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (N-methylben
Diroxycarbonylamino) valerylamino] -4-ph
Phenyl-2-butanone (Compound No. 299 of Table-1)
Manufacturing IR (neat, cm^-1): 3300, 1710, 16
95,1650 NMR (CDCl₃, Δ): 0.85 to 0.95 (m,
6H), 1.35 to 1.68 (m, 3H), 2.54
(S, 2H), 2.78 (s, 1H), 2.80-2.
98 (m, 1H), 3.0 to 3.25 (m, 3H),
3.64 (s, 0.7H), 3.67 (s, 1.3
H), 4.50 to 4.75 (m, 1H), 4.95.
(M, 1H), 5.13 (s, 2H), 6.19 (d,
J = 2.9 Hz, 1H), 6.28 (m, 1H), 6.
55 (d, J = 7 Hz, 0.7 H), 6.95 to 7.4
0 (m, 11.3H) Example 143 (s) -3-[(s) -2
-(2-chlorobenzyloxycarbonylamino) -4-
Methylvalerylamino] -1-furfurylthio-4-fur
Phenyl-2-butanone (Compound No. 301 in Table-1)
Manufacturing Melting point: 80-85 ° C IR (KBr, cm^-1): 3340, 3290, 173
5,1698,1660 NMR (CDCl₃, Δ): 0.83 to 0.98 (m,
6H), 1.35 to 1.70 (m, 3H), 2.98
(Dd, J = 7.2Hz, 14Hz, 1H), 3.05
~ 3.23 (m, 3H), 3.63 (s, 2H), 4.
15 (m, 1H), 4.93 to 5.03 (m, 2H),
5.21 (s, 2H), 6.17 (d, J = 3.2H
z, 1H), 6.29 (m, 1H), 6.58 (d, J
= 7 Hz, 1H), 7.05 to 7.45 (m, 10H) Example 144 (s) -3-[(s) -2
-(4-chlorobenzyloxycarbonylamino) -4-
Methylvalerylamino] -1-furfurylthio-4-fur
Phenyl-2-butanone (Compound No. 303 of Table-1)
Manufacturing Melting point: 123-124 ° C IR (KBr, cm^-1): 3350, 3310, 173
2,1698,1663 NMR (CDCl₃, Δ): 0.89 (d, J = 6.1)
Hz, 6H), 1.33 to 1.70 (m, 3H), 2.
98 (dd, J = 6.8 Hz, 14 Hz, 1 H), 3.
05-3.25 (m, 3H), 3.63 (s, 2H),
4.13 (m, 1H), 4.90 to 5.12 (m, 2)
H), 5.05 (s, 2H), 6.19 (d, J = 3.
2Hz, 1H), 6.27 (m, 1H), 6.53
(D, J = 7 Hz, 1H), 7.11 (d, J = 6.7)
Hz, 2H), 7.15 to 7.38 (m, 8H) Example 145 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (1,2,3,4
-Tetrahydro-1-naphthoxycarbonylamino) va
Relylamino] -4-phenyl-2-butanone (Table-1
Compound No. 308) of IR (KBr, cm^-1): 3300, 1715, 167
5,1655 NMR (CDCl₃, Δ): 0.85-1.0 (m, 6
H), 1.30 to 1.70 (m, 3H), 1.70 to
2.10 (m, 4H), 2.65 to 3.30 (m, 6
H), 3.64 (s, 2H), 4.15 (m, 1H),
4.89 (d, J = 7.6Hz, 1H), 5.01
(M, 1H), 5.87 (m, 1H), 6.20 (d,
J = 3.1 Hz, 1H), 6.30 (m, 1H), 6.
64 (d, J = 6.2 Hz, 1H), 7.10 to 7.3
6 (m, 10H) Example 146 (s) -3-[(s) -2
-(9-Fluorenylmethoxycarbonylamino) -4
-Methylvalerylamino] -1-furfurylthio-4-
Phenyl-2-butanone (Compound No. 309 of Table-1)
Manufacturing of IR (KBr, cm^-1): 3320, 3280, 168
0,1660 NMR (CDCl₃, Δ): 0.83 to 0.98 (m,
6H), 1.40 to 1.70 (m, 3H), 2.98
(M, 1H), 3.08 to 3.20 (m, 3H), 3.
62 (s, 2H), 4.05 to 4.30 (m, 2H),
4.30-4.50 (m, 2H), 4.90-5.15
(M, 2H), 6.18 (m, 1H), 6.28 (m,
1H), 6.52 (m, 1H), 7.10 to 7.50
(M, 10H), 7.58 (d, J = 7.3 Hz, 2
H), 7.77 (d, J = 7.3 Hz, 2H) Example 147 (s) -1-furfurylchi
O-3-((s) -4-methyl-2-tetrahydrofur
Furyloxycarbonylaminovalerylamino) -4-
Phenyl-2-butanone (Compound No. 310 in Table-1)
Manufacturing of IR (neat, cm^-1): 3320, 1710, 16
Fifty NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 6)
H), 1.20 to 1.70 (m, 5H), 1.84 to
2.04 (m, 2H), 2.98 (dd, J = 8.2H
z, 15 Hz, 1H), 3.10 to 3.25 (m, 3
H), 3.63 (s, 2H), 3.66 to 4.0 (m,
3H), 4.0-4.22 (m, 3H), 4.96-
5.08 (m, 2H), 6.19 (m, 1H), 6.2
9 (m, 1H), 6.64 (m, 1H), 7.15 ~
7.40 (m, 6H) Example 148 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-tetrahydr
Lopyranylmethoxycarbonylamino) valerylami
No] -4-phenyl-2-butanone (compound number in Table-1
No. 311) IR (KBr, cm^-1): 3300, 1720, 168
0,1650 NMR (CDCl₃, Δ): 0.80 to 1.0 (m, 6)
H), 1.23 to 1.90 (m, 9H), 2.97 (d
d, J = 7.3 Hz, 14 Hz, 1H), 3.08-
3.26 (m, 3H), 3.38 to 3.70 (m, 2)
H), 3.63 (s, 2H), 3.90-4.17.
(M, 4H), 4.92 to 5.08 (m, 2H), 6.
19 (m, 1H), 6.29 (m, 1H), 6.62
(D, J = 7 Hz, 1H), 7.05 to 7.40 (m,
6H) Example 149 (s) -3-((s) -2
-Furfuryloxycarbonylamino-4-methylvale
Rylamino) -1-furfurylthio-4-phenyl-2
-Production of butanone (compound number 312 of Table-1) Melting point: 115 to 118 ° C IR (KBr, cm^-1): 3350, 3300, 173
0,1695,1666 NMR (CDCl₃, Δ): 0.89 (d, J = 6.2)
Hz, 6H), 1.28 to 1.65 (m, 3H), 3.
01 (dd, J = 6.5 Hz, 15 Hz, 1 H), 3.
08-3.27 (m, 3H), 3.63 (s, 2H),
4.12 (m, 1H), 4.86 to 5.07 (m, 2
H), 5.05 (s, 2H), 6.19 (d, J = 2.
9 Hz, 1H), 6.29 (m, 1H), 6.36
(M, 1H), 6.41 (d, J = 3.2Hz, 1
H), 6.54 (m, 1H), 7.13 (d, J = 7.
8 Hz, 2H), 7.18 to 7.32 (m, 3H),
7.35 (m, 1H), 7.42 (s, 1H) Example 150 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-pyridylme
Toxycarbonylamino) valerylamino] -4-phen
Production of Nil-2-butanone (Compound No. 313 of Table-1)
Construction Melting point: 93-94 ° C IR (KBr, cm^-1): 3350, 3300, 173
3,1698,1658 NMR (CDCl₃, Δ): 0.89 (d, J = 6.4)
Hz, 3H), 0.91 (d, J = 6.1Hz, 3
H), 1.33 to 1.75 (m, 3H), 2.98 (d
d, J = 6.5 Hz, 14 Hz, 1H), 3.08-
3.27 (m, 3H), 3.62 (s, 2H), 4.1
4 (m, 1H), 4.98 (q, J = 6.5 Hz, 1
H), 5.10-5.30 (m, 1H), 5.21
(S, 2H), 6.17 (d, J = 3.2Hz, 1
H), 6.29 (m, 1H), 6.65 (d, J = 7H
z, 1H), 7.07 to 7.38 (m, 8H), 7.7.
2 (t, J = 8.3 Hz, 1 H), 8.57 (d, J =
5.0Hz, 1H) Example 151 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (3-pyridylme
Toxycarbonylamino) valerylamino] -4-phen
Preparation of Nil-2-butanone (Compound No. 315 of Table-1)
Construction IR (neat, cm^-1): 3320, 1720, 16
98,1600 NMR (CDCl₃, Δ): 0.90 (d, J = 6.2)
Hz, 6H), 1.33 to 1.72 (m, 3H), 2.
98 (dd, J = 6.7 Hz, 14 Hz, 1 H), 3.
08-3.27 (m, 3H), 3.63 (s, 2H),
4.12 (m, 1H), 5.01 (q, J = 7.5H
z, 1H), 5.0 to 5.20 (m, 1H), 5.11
(S, 2H), 6.19 (d, J = 3.0Hz, 1
H), 6.29 (m, 1H), 6.53 (m, 1H),
7.13 (d, J = 7.7Hz, 2H), 7.18-
7.37 (m, 5H), 7.68 (d, J = 8Hz, 1
H), 8.52 to 8.63 (m, 2H) Example 152 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-pyridylme
Toxycarbonylamino) valerylamino] -4-phen
Preparation of Nil-2-butanone (Compound No. 317 of Table-1)
Construction IR (neat, cm^-1): 3320, 1718, 16
63 NMR (CDCl₃, Δ): 0.90 to 1.02 (m,
6H), 1.36 to 1.75 (m, 3H), 3.04
(Dd, J = 6.7Hz, 14Hz, 1H), 3.07
~ 3.24 (m, 3H), 3.63 (s, 2H), 4.
13 (m, 1H), 5.03 (q, J = 6.7Hz, 1
H), 5.10 (s, 2H), 5.30 (d, J = 7H)
z, 1H), 6.19 (d, J = 2.9Hz, 1H),
6.29 (m, 1H), 6.67 (d, J = 7 Hz, 1
H), 7.08 to 7.33 (m, 7H), 7.35.
(M, 1H), 8.59 (d, J = 7.5Hz, 2H) Example 153 (s) -3-((s) -2
-Amino-4-methylvalerylamino) -1-furfuri
Ruthio-4-phenyl-2-butanone hydrochloride (Table 1
Compound No. 323) of IR (KBr, cm^-1): 3400, 1700, 165
5 NMR (D₂O, δ): 0.65 to 0.85 (m, 6)
H), 1.30 to 1.50 (m, 3H), 2.73 (d
d, J = 9.2 Hz, 14 Hz, 1 H), 3.02 (d
d, J = 7.5 Hz, 14 Hz, 1H), 3.28
(D, J = 15 Hz, 1H), 3.42 (d, J = 15
Hz, 1H), 3.55 (s, 2H), 3.73 (m,
1H), 4.67 (m, 1H), 6.08 (d, J =
2.8 Hz, 1H), 6.20 (m, 1H), 6.95
~ 7.30 (m, 5H), 7.28 (m, 1H) Example 154 (s) -1-furfurylchi
O-3-((s) -2-isovalerylamino-4-methyl
Luvalerylamino) -4-phenyl-2-butanone (Table
-1 Compound No. 325) Melting point: 108-115 ° C IR (KBr, cm^-1): 3310, 1715, 164
0 NMR (CDCl₃, Δ): 0.93 to 1.06 (m,
12H), 1.40 to 1.75 (m, 4H), 1.95.
˜2.20 (m, 2H), 2.98 (dd, J = 7.2)
Hz, 14 Hz, 1H), 3.16 (dd, J = 6.7)
Hz, 14 Hz, 1H), 3.16 (s, 2H), 3.
65 (s, 2H), 4.43 (m, 1H), 4.98
(M, 1H), 5.70 (d, J = 7Hz, 1H),
6.18 (d, J = 2.6 Hz, 1H), 6.29
(M, 1H), 6.70 (d, J = 7Hz, 1H),
7.08-7.38 (m, 6H) Example 155 (s) -3-[(s) -2
-(3-Cyclohexylpropionylamino) -4-me
Cylvalerylamino] -1-furfurylthio-4-phen
Production of Nil-2-butanone (Compound No. 328 of Table-1)
Construction Melting point: 116-118 ° C IR (KBr, cm^-1): 3300, 1722, 171
0,1638 NMR (CDCl₃ , Δ): 0.80 to 1.0 (m, 8)
H), 1.08 to 1.80 (m, 14H), 2.15
(T, J = 7.8 Hz, 2H), 2.98 (dd, J =
7.3 Hz, 14 Hz, 1 H), 3.15 (dd, J =
5.3Hz, 14Hz, 1H), 3.16 (s, 2
H), 3.64 (s, 2H), 4.40 (m, 1H),
4.97 (q, J = 7.2 Hz, 1H), 5.66
(D, J = 7 Hz, 1 H), 6.19 (d, J = 3.1)
Hz, 1H), 6.29 (m, 1H), 6.66 (d,
J = 7 Hz, 1H), 7.13 to 7.38 (m, 6H) Example 156 (s) -3-[(s) -2
-(4-Cyclohexylbutyrylamino) -4-methyl
Valerylamino] -1-furfurylthio-4-phenyl
Preparation of 2-butanone (Compound No. 329 of Table-1) IR (KBr, cm^-1): 3270, 1730, 165
0,1640 NMR (CDCl₃ , Δ): 0.75 to 1.03 (m,
8H), 1.03 to 1.75 (m, 16H), 2.11.
(T, J = 7.8 Hz, 2H), 2.98 (dd, J =
7.2 Hz, 14 Hz, 1 H), 3.11 (dd, J =
6.5Hz, 14Hz, 1H), 3.16 (s, 2
H), 3.64 (s, 2H), 4.41 (m, 1H),
4.98 (m, 1H), 5.67 (d, J = 8Hz, 1
H), 6.19 (d, J = 3.0 Hz, 1H), 6.2
9 (m, 1H), 6.69 (d, J = 7Hz, 1H),
7.10-7.37 (m, 6H) Example 157 (s) -1-furfurylchi
O-3- [4-methyl-2- (3-phenylpropioni)
Lumino) valerylamino] -4-phenyl-2-buta
Production of Non (Compound No. 331 of Table-1) Melting point: 117-119 ° C IR (KBr, cm^-1): 3320, 1730, 171
0,1643 NMR (CDCl₃ , Δ): 0.83 (d, J = 6.2)
Hz, 3H), 0.85 (d, J = 6.2Hz, 3
H), 1.25 to 1.65 (m, 3H), 2.33 to
2.53 (m, 2H), 2.85 to 3.03 (m, 3
H), 3.05 to 3.18 (m, 1H), 3.15.
(S, 2H), 3.64 (s, 2H), 4.35 (m,
1H), 4.96 (q, J = 6.7Hz, 1H), 5.
53 (d, J = 7 Hz, 1 H), 6.19 (d, J =
3.3 Hz, 1H), 6.30 (m, 1H), 6.58
(D, J = 7 Hz, 1 H), 7.10 to 7.40 (m,
11H) Example 158 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-phenylbutane
Tyrylamino) valerylamino] -4-phenyl-2-
Production of butanone (Compound No. 332 of Table-1) Melting point: 106-108 ° C IR (KBr, cm^-1): 3300, 1728, 170
8,1638 NMR (CDCl₃ , Δ): 0.89 (d, J = 5.9)
Hz, 3H), 0.91 (d, J = 6.1Hz, 3
H), 1.40 to 1.65 (m, 3H), 1.85
2.05 (m, 2H), 2.14 (t, J = 7.4H
z, 2H), 2.63 (t, J = 7.3 Hz, 2H),
2.96 (dd, J = 7.4 Hz, 14 Hz, 1 H),
3.15 (dd, J = 7.5Hz, 14Hz, 1H),
3.16 (s, 2H), 3.63 (s, 2H), 4.4
0 (m, 1H), 4.98 (d, J = 6.6 Hz, 1
H), 5.64 (d, J = 7 Hz, 1H), 6.18
(D, J = 3.2 Hz, 1H), 6.29 (m, 1
H), 6.63 (d, J = 7 Hz, 1H), 7.10
7.40 (m, 11H) Example 159 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (1-naphthyla
Cetylamino) valerylamino] -4-phenyl-2-
Production of butanone (Compound No. 333 of Table-1) Melting point: 143-146 ° C IR (KBr, cm^-1): 3300, 1715, 165
0 NMR (CDCl₃ , Δ): 0.64 (d, J = 6.8)
Hz, 3H), 0.66 (d, J = 6.8Hz, 3
H), 0.98 to 1.15 (m, 2H), 1.25 to
1.45 (m, 1H), 2.78 (dd, J = 7.9H
z, 14 Hz, 1H), 3.07 (dd, J = 6.5H
z, 14 Hz, 1H), 3.14 (d, J = 1.7H)
z, 2H), 3.64 (s, 2H), 3.93 (d, J
= 16 Hz, 1 H), 4.04 (d, J = 16 Hz, 1
H), 4.29 (m, 1H), 4.86 (m, 1H),
5.37 (d, J = 7 Hz, 1H), 6.19 (d, J
= 2.9 Hz, 1H), 6.29 (m, 1H), 6.5
3 (d, J = 8 Hz, 1H), 6.95 to 7.10
(M, 2H), 7.20 to 7.30 (m, 5H), 7.
30 to 7.40 (m, 2H), 7.45 to 7.60
(M, 3H), 7.87 (m, 1H) Example 160 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-naphthyla
Cetylamino) valerylamino] -4-phenyl-2-
Production of butanone (Compound No. 334 of Table-1) Melting point: 123-125 ° C IR (KBr, cm^-1): 3320, 3300, 171
5,1640 NMR (CDCl₃ , Δ): 0.73 to 0.90 (m,
6H), 1.20 to 1.70 (m, 3H), 2.91.
(Dd, J = 7.7Hz, 14Hz, 1H), 3.09
(Dd, J = 7.7 Hz, 14 Hz, 1 H), 3.14
(S, 2H), 3.63 (s, 2H), 3.69 (d,
J = 3.1 Hz, 2H), 4.37 (m, 1H), 4.
93 (m, 1H), 5.60 (d, J = 8.3 Hz, 1
H), 6.18 (d, J = 3.1 Hz, 1H), 6.2
8 (m, 1H), 6.62 (d, J = 7.5 Hz, 1
H), 7.05 to 7.16 (m, 2H), 7.20 to
7.35 (m, 5H), 7.45 to 7.55 (m, 2
H), 7.67 (s, 1H), 7.74 to 7.90.
(M, 3H) Example 161 (s) -3-((s) -2
-Cinnamoylamino-4-methylvalerylamino)-
1-furfurylthio-4-phenyl-2-butanone (Table
-1 Compound No. 335) Melting point: 141-143 ° C IR (KBr, cm^-1): 3300, 1730, 171
0, 1650, 1623 NMR (CDCl₃ , Δ): 0.93 (d, J = 4.3)
Hz, 6H), 1.43 to 1.78 (m, 3H), 2.
95 (dd, J = 7.5 Hz, 15 Hz, 1 H), 3.
15 (dd, J = 7.5 Hz, 15 Hz, 1 H), 3.
19 (s, 2H), 3.65 (s, 2H), 4.59
(M, 1H), 5.0 (q, J = 6.6Hz, 1H),
5.94 (d, J = 8 Hz, 1H), 6.19 (d, J
= 3.3 Hz, 1H), 6.29 (m, 1H), 6.3
5 (d, J = 16Hz, 1H), 6.82 (d, J = 8)
Hz, 1H), 7.10 to 7.30 (m, 5H), 7.
30 to 7.45 (m, 4H), 7.45 to 7.55
(M, 2H), 7.63 (d, J = 16Hz, 1H) Example 162 (s) -3-[(s) -2
-(3-Benzothienylacetylamino) -4-methyl
Valerylamino] -1-furfurylthio-4-phenyl
Preparation of 2-butanone (Compound No. 345 of Table-1) Melting point: 150-153 ° C IR (KBr, cm^-1): 3300, 1710, 164
0 NMR (CDCl₃ , Δ): 0.65 to 0.80 (m,
6H), 1.13 to 1.28 (m, 2H), 1.35
1.55 (m, 1H), 2.83 (dd, J = 7.7H
z, 18 Hz, 1H), 3.07 (dd, J = 7.7H
z, 18 Hz, 1H), 3.14 (s, 2H), 3.6
3 (s, 2H), 3.78 (s, 2H), 4.30-
4.45 (m, 1H), 4.59 (q, J = 6.7H
z, 1H), 5.68 (d, J = 8Hz, 1H), 6.
18 (d, J = 3.2 Hz, 1H), 6.27 to 6.3.
4 (m, 1H), 6.63 (d, J = 8Hz, 1H),
7.05 to 7.15 (m, 2H), 7.20 to 7.48
(M, 7H), 7.65 to 7.78 (m, 1H), 7.
85-7.97 (m, 1H) Example 163 (s) -3-((s) -2
-Cyclohexyloxyacetylamino-4-methylva
Relylamino) -1-furfurylthio-4-phenyl-
Preparation of 2-butanone (Compound No. 347 of Table-1) IR (neat, cm^-1): 3300, 1700, 16
Fifty NMR (CDCl₃ , Δ): 0.87 to 0.92 (m,
6H), 1.18 to 1.90 (m, 13H), 2.97.
(Dd, J = 7.6 Hz, 14 Hz, 1 H), 3.14
(Dd, J = 6.3 Hz, 14 Hz, 1 H), 3.14
(D, J = 15 Hz, 1H), 3.21 (d, J = 15
Hz, 1H), 3.28 (m, 1H), 3.64 (s,
2H), 3.86 (d, J = 16Hz, 1H), 3.9
5 (d, J = 16 Hz, 1 H), 4.39 (m, 1
H), 4.97 (q, J = 7.5 Hz, 1H), 6.1
9 (d, J = 2.9 Hz, 1H), 6.29 (m, 1
H), 6.76 (d, J = 8 Hz, 1H), 6.80
(D, J = 8 Hz, 1 H), 7.13 to 7.36 (m,
6H) Example 164 (s) -1-furfurylchi
O-3-((s) -4-methyl-2-phenoxyacetyl
Luminovalerylamino) -4-phenyl-2-butano
(Compound No. 348 of Table-1) Melting point: 91-95 ° C IR (KBr, cm^-1): 3300, 3270, 173
5,1650 NMR (CDCl₃ , Δ): 0.80 to 0.95 (m,
6H), 1.30 to 1.75 (m, 3H), 2.95
(Dd, J = 7.7 Hz, 14 Hz, 1 H), 3.14
(Dd, J = 6.4 Hz, 14 Hz, 1H), 3.19
(D, J = 1.9 Hz, 2H), 3.66 (s, 2
H), 4.39 (d, J = 15 Hz, 1H), 4.47
(M, 1H), 4.49 (d, J = 15Hz, 1H),
5.0 (q, J = 7.4 Hz, 1H), 6.20 (d,
J = 2.9 Hz, 1H), 6.29 (m, 1H), 6.
60 (d, J = 7 Hz, 1H), 6.73 (d, J = 8
Hz, 1H), 6.91 (d, J = 8.8Hz, 2
H), 7.0 to 7.36 (m, 9H) Example 165 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-phenoxy
Propionylamino) valerylamino] -4-phenyl
Preparation of 2-butanone (Compound No. 349 of Table-1) IR (KBr, cm^-1): 3280, 1710, 164
0 NMR (CDCl₃ , Δ): 0.75 (d, J = 6.5)
Hz, 3H), 0.89 (d, J = 6.6Hz, 1.5
H), 0.91 (d, J = 6.6Hz, 1.5H),
1.05 to 1.70 (m, 6H), 2.76 (dd, J
= 7.9 Hz, 14 Hz, 0.5 H), 2.93-3.
20 (m, 3.5H), 3.64 (s, 2H), 4.3
7 (m, 1H), 4.67 (m, 1H), 4.87
(Q, J = 7.3 Hz, 0.5 H), 4.99 (q, J
= 7.3 Hz, 0.5 H), 6.19 (m, 1 H),
6.29 (m, 1H), 6.42 (d, J = 8 Hz,
0.5H), 6.62 to 6.67 (m, 1.5H),
6.86-6.93 (m, 2H), 6.99-7.06
(M, 2H), 7.13 to 7.36 (m, 7H) Example 166 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-phenoxy
Butyrylamino) valerylamino] -4-phenyl-2
-Production of butanone (Compound No. 350 of Table-1) IR (KBr, cm^-1): 3260, 1720, 170
5,1640 NMR (CDCl₃ , Δ): 0.73 (d, J = 6.5)
Hz, 3H), 0.80 to 0.96 (m, 3H), 0.
96-1.10 (m, 3H), 1.20-1.65
(M, 3H), 1.75 to 2.05 (m, 2H), 2.
73 (dd, J = 8.1 Hz, 14 Hz, 0.5 H),
2.86-3.20 (m, 1.5H), 3.14 (s,
2H), 3.63 (s, 2H), 4.37 (m, 1
H), 4.53 (m, 1H), 4.85 (q, J = 5.
0Hz, 0.5H), 4.99 (q, J = 5.0Hz,
0.5H), 6.19 (m, 1H), 6.29 (m, 1)
H), 6.43 (d, J = 8Hz, 0.5H), 6.5
2 (d, J = 8 Hz, 0.5 H), 6.55 (d, J =
8 Hz, 0.5 H), 6.64 (d, J = 8 Hz, 0.
5H), 6.84-6.96 (m, 2H), 6.96-
7.05 (m, 2H), 7.05 to 7.40 (m, 7
H) Example 167 (s) -3-[(s) -2
-(2-Chlorophenoxyacetylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-4-phenyl
Preparation of Le-2-butanone (Compound No. 354 of Table-1) Melting point: 99 to 102 ° C IR (KBr, cm^-1): 3300, 1710, 167
0,1640 NMR (CDCl₃ , Δ): 0.85 to 0.95 (m,
6H), 1.42 to 1.75 (m, 3H), 2.97.
(Dd, J = 7.5 Hz, 14 Hz, 1H), 3.16
(Dd, J = 5.3Hz, 14Hz, 1H), 3.16
(D, J = 15 Hz, 1H), 3.23 (d, J = 15
Hz, 1H), 3.65 (s, 2H), 4.24 (m,
1H), 4.43 (d, J = 15Hz, 1H), 4.5
1 (d, J = 15 Hz, 1H), 5.02 (q, J =
7.5 Hz, 1 H), 6.19 (d, J = 2.9 Hz,
1H), 6.29 (m, 1H), 6.67 (d, J = 8)
Hz, 1H), 6.88 (d, J = 8Hz, 1H),
6.95-7.45 (m, 10H) Example 168 (s) -3-[(s) -2
-(4-Chlorophenoxyacetylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-4-phenyl
Preparation of le-2-butanone (Compound No. 356 of Table-1) Melting point: 116-117 ° C IR (KBr, cm^-1): 3300, 3250, 173
0,1670,1650 NMR (CDCl₃ , Δ): 0.83 to 0.96 (m,
6H), 1.45 to 1.70 (m, 3H), 2.96
(Dd, J = 7.6 Hz, 14 Hz, 1 H), 3.11
(Dd, J = 6.4 Hz, 14 Hz, 1H), 3.19
(S, 2H), 3.66 (s, 2H), 4.35 (d,
J = 15Hz, 1H), 4.46 (d, J = 15Hz,
1H), 4.44 (m, 1H), 5.01 (dd, J =
7.5Hz, 14Hz, 1H), 6.20 (m, 1
H), 6.30 (m, 1H), 6.58 (d, J = 8H
z, 1H), 6.71 (d, J = 9Hz, 1H), 6.
80-6.86 (m, 2H), 7.11-7.36
(M, 8H) Example 169 (s) -1-furfurylchi
O-3-[(s) -2- (2-methoxyphenoxyacetate
Cylamino) -4-methylvalerylamino] -4-phen
Preparation of Nil-2-butanone (Compound No. 361 of Table-1)
Construction IR (KBr, cm^-1): 3280, 1705, 166
5,1645 NMR (CDCl₃ , Δ): 0.87 (d, J = 6.7)
Hz, 3H), 0.89 (d, J = 6.7Hz, 3
H), 1.39 to 1.71 (m, 3H), 2.91 (d
d, J = 7.7 Hz, 14 Hz, 1 H), 3.10 (d
d, J = 7.7 Hz, 14 Hz, 1H), 3.13
(D, J = 17 Hz, 1H), 3.21 (d, J = 17
Hz, 1H), 3.64 (s, 2H), 3.86 (s,
3H), 4.42 (m, 1H), 4.45 (d, J = 1)
5Hz, 1H), 4.55 (d, J = 15Hz, 1
H), 4.95 (q, J = 6.4 Hz, 1H), 4.8
5 to 5.05 (m, 1H), 6.20 (m, 1H),
6.29 (m, 1H), 6.70 (d, J = 7.1H
z, 1H), 6.90 to 7.0 (m, 3H), 7.0
7.40 (m, 7H) Example 170 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (1-naphthoxy
Acetylamino) valerylamino] -4-phenyl-2
-Production of butanone (Compound No. 364 of Table-1) Melting point: 118-120 ° C IR (KBr, cm^-1): 3300, 1730, 167
0,1650 NMR (CDCl₃ , Δ): 0.75 to 1.03 (m,
6H), 1.38 to 1.65 (m, 3H), 2.95.
(Dd, J = 7.8Hz, 14Hz, 1H), 3.15
(Dd, J = 6.4 Hz, 14 Hz, 1H), 3.19
(S, 2H), 3.66 (s, 2H), 4.50 (m,
1H), 4.61 (d, J = 15Hz, 1H), 4.6
9 (d, J = 15 Hz, 1 H), 5.04 (q, J =
7.0 Hz, 1 H), 6.20 (d, J = 3.1 Hz,
1H), 6.29 (m, 1H), 6.62 (d, J =
7.1 Hz, 1 H), 6.70 to 6.90 (m, 2
H), 7.0 to 7.65 (m, 10H), 7.84
(M, 1H), 8.18 (m, 1H) Example 171 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-naphthoxy
Acetylamino) valerylamino] -4-phenyl-2
-Production of butanone (Compound No. 365 of Table-1) IR (KBr, cm^-1): 3300, 1710, 167
5,1650 NMR (CDCl₃ , Δ): 0.86 (d, J = 6.1)
Hz, 6H), 1.45 to 1.70 (m, 3H), 2.
95 (dd, J = 7.6 Hz, 14 Hz, 1 H), 3.
12 (dd, J = 6.5 Hz, 14 Hz, 1 H), 3.
18 (d, J = 1.8 Hz, 2H), 3.66 (s, 2
H), 4.50 (m, 1H), 4.52 (d, J = 15)
Hz, 1H), 4.61 (d, J = 15Hz, 1H),
5.0 (q, J = 6.5 Hz, 1H), 6.20 (m,
1H), 6.29 (m, 1H), 6.62 (d, J = 8)
Hz, 1H), 6.79 (d, J = 8.5Hz, 1
H), 7.10 to 7.30 (m, 7H), 7.30 to
7.52 (m, 3H), 7.70 to 7.90 (m, 3)
H) Example 172 (s) -3-((s) -2
-Benzyloxyacetylamino-4-methylvaleryl lua
Mino) -1-furfurylthio-4-phenyl-2-buta
Production of Non (Compound No. 366 of Table-1) IR (KBr, cm^-1): 3350, 3310, 169
0,1640 NMR (CDCl₃ , Δ): 0.89 (d, J = 5.7)
Hz, 3H), 0.91 (d, J = 5.7Hz, 3
H), 1.46 to 1.70 (m, 3H), 2.96 (d
d, J = 7.7 Hz, 14 Hz, 1 H), 3.14 (d
d, J = 6.4 Hz, 14 Hz, 1H), 3.17
(D, J = 2.7 Hz, 2H), 3.64 (s, 2
H), 3.88 (d, J = 14 Hz, 1H), 3.96.
(D, J = 14 Hz, 1H), 4.41 (m, 1H),
4.55 (s, 2H), 4.98 (q, J = 6.6H
z, 1H), 6.19 (m, 1H), 6.29 (m, 1)
H), 6.69 (d, J = 8Hz, 1H), 6.78
(D, J = 8 Hz, 1H), 7.10 to 7.42 (m,
11H) Example 173 (s) -1-furfuryl
O-3-[(s) -4-methyl-2- (2-tetrahydr
Lopyranyloxyacetylamino) valerylamino]-
4-phenyl-2-butanone (Compound No. 37 in Table 1
0) Manufacturing IR (neat, cm^-1): 3300, 1710, 16
60 NMR (CDCl₃ , Δ): 0.85 to 0.95 (m,
6H), 1.40 to 1.88 (m, 9H), 2.97.
(M, 1H), 3.13 (m, 1H), 3.19 (m,
2H), 3.50 (m, 1H), 3.64 (s, 2
H), 3.78 (m, 1H), 3.91 to 4.20.
(M, 2H), 4.42 (m, 1H), 4.55 (m,
1H), 4.97 (m, 1H), 6.19 (m, 1
H), 6.29 (m, 1H), 6.30 to 6.85.
(M, 2H), 7.10 to 7.36 (m, 6H) Example 174 (s) -3-[(s) -2
-(2-Benzofuranylcarbonylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-4-phenyl
Preparation of le-2-butanone (Compound No. 382 of Table-1) IR (KBr, cm^-1): 3300, 1720, 164
0 NMR (CDCl₃ , Δ): 0.90 to 1.0 (m, 6)
H), 1.55 to 1.80 (m, 3H), 2.97 (d
d, J = 7.6 Hz, 14 Hz, 1 H), 3.13 (d
d, J = 6.4 Hz, 14 Hz, 1H), 3.20
(S, 2H), 3.66 (s, 2H), 4.63 (m,
1H), 5.04 (q, J = 7.4Hz, 1H), 6.
20 (m, 1H), 6.29 (m, 1H), 6.68
(D, J = 8 Hz, 1H), 6.82 (d, J = 8H
z, 1H), 7.02 to 7.20 (m, 5H), 7.2
7 to 7.36 (m, 2H), 7.40 to 7.55 (m,
3H), 7.70 (d, J = 7.9Hz, 1H) Example 175 (s) -3-[(s) -2
-(2-Chromanylcarbonylamino) -4-methylva
Lerylamino] -1-furfurylthio-4-phenyl-
Preparation of 2-butanone (Compound No. 384 of Table-1) IR (KBr, cm^-1): 3300, 1730, 165
0 NMR (CDCl₃ , Δ): 0.78 to 0.85 (m,
3H), 0.93 (d, J = 6.3Hz, 1.5H),
0.95 (d, J = 6.3Hz, 1.5H), 1.22
~ 1.78 (m, 3H), 1.78 to 2.15 (m, 1
H), 2.28 to 2.45 (m, 1H), 2.66 to
3.13 (m, 4H), 3.13 to 3.20 (m, 2)
H), 3.63 (s, 1H), 3.65 (s, 1H),
4.35 to 4.54 (m, 2H), 4.90 to 5.08
(M, 1H), 6.18 to 6.22 (m, 1H), 6.
30 to 6.34 (m, 1H), 6.51 (d, J = 8H
z, 0.5H), 6.70 (d, J = 8Hz, 0.5
H), 6.76 (d, J = 9 Hz, 0.5H), 6.8
3 (d, J = 8 Hz, 0.5 H), 6.87 to 6.94
(M, 2H), 7.04 to 7.36 (m, 8H) Example 176 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-oxo-4)
H-1-benzopyran-2-ylcarbonylamino) va
Relylamino] 4-phenyl-2-butanone (Table 1
Production of compound No. 386) IR (neat, cm^-1): 3320, 1710, 16
Fifty NMR (CDCl₃ , Δ): 0.95 to 0.98 (m,
6H), 1.62 to 1.80 (m, 3H), 2.98.
(Dd, J = 7.5 Hz, 14 Hz, 1H), 3.16
(Dd, J = 6.4 Hz, 14 Hz, 1 H), 3.21
(S, 2H), 3.64 (s, 2H), 4.62 (m,
1H), 5.08 (q, J = 6.6Hz, 1H), 6.
20 (m, 1H), 6.30 (m, 1H), 6.56
(D, J = 8 Hz, 1H), 7.06 to 7.26 (m,
7H), 7.36 (m, 1H), 7.44 to 7.60.
(M, 2H), 7.70 to 7.82 (m, 1H), 8.
24 (dd, J = 1.7Hz, 7.9Hz, 1H) Example 177 (s) -3-[(s) -2
-(3-Benzylureido) -4-methylvalerylami
No] -1-furfurylthio-4-phenyl-2-butano
(Compound No. 388 of Table-1) Melting point: 95-97 ° C IR (KBr, cm^-1): 3310, 1708, 165
0,1628 NMR (CDCl₃ , Δ): 0.87 (d, J = 4.9)
Hz, 6H), 1.30 to 1.70 (m, 3H), 2.
93 (dd, J = 6.5 Hz, 14 Hz, 1 H), 2.
98-3.19 (m, 3H), 3.58 (s, 2H),
4.17-4.45 (m, 3H), 4.87 (q, J =
6.5 Hz, 1 H), 5.17 to 5.35 (m, 2
H), 6.16 (d, J = 3.1 Hz, 1H), 6.2
8 (m, 1H), 6.95 to 7.38 (m, 12H) Example 178 (s) -3-((s) -2
-Benzyloxycarbonylamino-3-cyclohexyl
Propionylamino) -1-furfurylthio-4-phen
Preparation of Nil-2-butanone (Compound No. 400 in Table-1)
Construction Melting point: 124-125 ° C IR (KBr, cm^-1): 3350, 3310, 173
5,1690,1655 NMR (CDCl₃ , Δ: 0.78 to 1.0 (m, 2)
H), 1.0 to 1.45 (m, 6H), 1.45 to 1.
80 (m, 5H), 2.83 to 3.24 (m, 4H),
3.62 (s, 2H), 4.16 (m, 1H), 4.9
9 (q, J = 6.8 Hz, 1H), 5.10 (s, 2
H), 4.95 to 5.07 (m, 1H), 6.18.
(D, J = 2.8 Hz, 1H), 6.29 (m, 1
H), 6.58 (m, 1H), 7.03 to 7.42
(M, 11H) Example 179 (s) -3-((s) -2
-Benzyloxycarbonylamino-3-phenylpropyi
Onylamino) -1-furfurylthio-4-phenyl-
Preparation of 2-butanone (Compound No. 401 in Table-1) IR (KBr, cm^-1): 3300, 3260, 172
5,1685,1650 NMR (CDCl₃ , Δ): 2.91 (dd, J = 7.
1 Hz, 14 Hz, 1 H), 2.95-3.10 (m,
5H), 3.56 (s, 2H), 4.37 (m, 1
H), 4.95 (q, J = 7.4Hz, 1H), 5.0
8 (s, 2H), 5.13 (m, 1H), 6.17
(D, J = 2.5 Hz, 1 H), 6.29 (m, 1
H), 6.32 (d, J = 7 Hz, 1H), 7.0
7.04 (m, 2H), 7.10 to 7.35 (m, 14
H) Example 180 (s) -3- (2-benzo
Ilamino-2-methoxyacetylamino) -1-full
Furylthio-4-phenyl-2-butanone (Table 1
Production of compound number 404) IR (KBr, cm^-1): 3300, 1730, 167
0,1640 NMR (CDCl₃ , Δ): 3.04 (dd, J = 7.
0 Hz, 14 Hz, 1 H), 3.11 to 3.22 (m,
3H), 3.45 (s, 0.9H), 3.49 (s,
2.1H), 3.65 (s, 0.6H), 3.68
(S, 1.4H), 5.09 (m, 1H), 5.66
(D, J = 8 Hz, 0.7 H), 5.67 (d, J = 8
Hz, 0.3H), 6.20 (m, 1H), 6.30
(M, 1H), 6.87 (d, J = 8Hz, 0.3
H), 7.03 (d, J = 8Hz, 0.7H), 7.0
8 to 7.28 (m, 7H), 7.41 to 7.60 (m,
3H), 7.78 to 7.86 (m, 2H) Example 181 (s) -3- (2-benzyl)
Roxycarbonylamino-2-isopropoxyacetyl
Amino) -1-furfurylthio-4-phenyl-2-bu
Production of Tanone (Compound No. 405 of Table-1) IR (KBr, cm^-1): 3300, 1720, 169
5,1655 NMR (CDCl₃ , Δ): 1.05 to 1.24 (m,
6H), 2.98 to 3.20 (m, 2H), 3.13
(S, 1H), 3.21 (s, 1H), 3.63 (s,
1H), 3.65 (s, 1H), 3.96 (m, 1
H), 4.99 (m, 1H), 5.13 (s, 2H),
5.35 (m, 1H), 5.40 (d, J = 7 Hz,
0.5H), 5.57 (d, J = 7Hz, 0.5H),
6.19 (m, 1H), 6.29 (m, 1H), 7.0
7 to 7.40 (m, 12H) Example 182 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (5-methoxycarbonylfurfuryl thiol
E) -4-Phenyl-2-butanone (Compound number in Table-1
No. 413) manufacturing Melting point: 85-93 ° C IR (KBr, cm^-1): 3300, 1740 to 168
0,1658 NMR (CDCl₃ , Δ): 0.89 (d, J = 6.3)
Hz, 6H), 1.25 to 1.65 (m, 3H), 2.
86 to 3.03 (m, 1H), 3.05 to 3.38
(M, 2H), 3.42 (d, J = 14Hz, 1H),
3.65 (s, 2H), 3.87 (s, 3H), 4.0
8 to 4.23 (m, 1H), 4.95 to 5.15 (m,
4H), 6.31 (d, J = 3.5Hz, 1H), 6.
85-6.95 (m, 1H), 7.09 (d, J = 3.
5Hz, 1H), 7.13 to 7.45 (m, 10H) Example 183 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (5-chloro-2-thienylmethylthio
E) -4-Phenyl-2-butanone (Compound number in Table-1
No. 423) Melting point: 105-107 ° C IR (KBr, cm^-1): 3340, 3310, 172
8,1692,1650 NMR (CDCl₃ , Δ): 0.90 to 1.0 (m, 6)
H), 1.30 to 1.65 (m, 3H), 2.90 to
3.23 (m, 4H), 3.70 (s, 2H), 4.1
3 (m, 1H), 4.85-5.0 (m, 2H), 5.
09 (s, 2H), 6.53 (m, 1H), 6.60 ~
6.73 (m, 2H), 7.12 (d, J = 6.0H
z, 2H), 7.15 to 7.40 (m, 8H) Example 184 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4-phenyl-1- (2-pyridylmethylthio)
E) -2-butanone (Compound No. 428 of Table-1)
Construction Melting point: 82-87 ° C IR (KBr, cm^-1): 3330, 3280, 171
8, 1680, 1655 NMR (CDCl₃ , Δ): 0.89 (d, J = 6.2)
Hz, 6H), 1.30 to 1.70 (m, 3H), 2.
98 (dd, J = 4.8 Hz, 14 Hz, 1 H), 3.
14 (dd, J = 4.8 Hz, 14 Hz, 1 H), 3.
16 (d, J = 15 Hz, 1H), 3.31 (d, J =
15Hz, 1H), 3.75 (s, 2H), 4.13
(M, 1H), 5.0 (q, J = 7.4Hz, 1H),
5.08 (s, 2H), 4.93 to 5.15 (m, 1
H), 6.74 (d, J = 7 Hz, 1H), 7.10
7.42 (m, 12H), 7.65 (dt, J = 1.8)
Hz, 7.7 Hz, 1H), 8.52 (d, J = 4.9)
Hz, 1H) Example 185 (s) -1- (2-benz
Imidazolylmethylthio) -3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-4-Phenyl-2-butanone (Compound No. 4 in Table-1
34) Manufacturing Melting point: 125-129 ° C IR (KBr, cm^-1): 3300, 1710, 169
0,1653 NMR (CDCl₃ , Δ): 0.80 to 1.0 (m, 6)
H), 1.30 to 1.70 (m, 3H), 2.75 to
2.95 (m, 1H), 2.95 to 3.25 (m, 2
H), 3.25 to 3.55 (m, 1H), 3.73 to
4.08 (m, 2H), 4.10 to 4.25 (m, 1
H), 4.90 to 5.25 (m, 2H), 5.07
(S, 2H), 7.0 to 7.15 (m, 2H), 7.1
5 to 7.40 (m, 12H), 7.40 to 7.70
(M, 2H) Example 186 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (3,5-dimethyl-4-isoxazo
Rylmethylthio) -4-phenyl-2-butanone (Table-
1 Compound No. 438) IR (neat, cm^-1): 3320, 1720, 17
05, 1655 NMR (CDCl₃ , Δ): 0.90 (d, J = 5.8)
Hz, 6H), 1.30 to 1.65 (m, 3H), 2.
24 (s, 3H), 2.34 (s, 3H), 2.90-
3.10 (m, 4H), 3.35 (s, 2H), 4.1
2 (m, 1H), 4.93 to 5.13 (m, 2H),
5.09 (s, 2H), 6.63 (d, J = 8Hz, 1
H), 7.10 to 7.45 (m, 10H) Example 187 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-methyl-4-thiazolylmethylthio
E) -4-Phenyl-2-butanone (Compound number in Table-1
No. 443) manufacturing IR (neat, cm^-1): 3330, 1725, 17
05,1660 NMR (CDCl₃ , Δ): 0.89 (d, J = 5.9)
Hz, 6H), 1.30 to 1.70 (m, 3H), 2.
68 (s, 3H), 2.95 to 3.07 (m, 1H),
3.07 to 3.30 (m, 3H), 3.69 (s, 2
H), 4.05 to 4.20 (m, 1H), 4.93 to
5.20 (m, 2H), 5.09 (s, 2H), 6.5
8 to 6.78 (m, 1H), 6.94 (s, 1H),
7.08 to 7.50 (m, 10H) Example 188 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-oxo-4-oxazolidinylme
Tylthio) -4-phenyl-2-butanone (Table 1
Production of compound number 445) IR (neat, cm^-1): 3330, 1705, 16
95, 1655 NMR (CDCl₃ , Δ): 0.78 to 0.95 (m,
6H), 1.20 to 1.75 (m, 3H), 2.40 to
2.62 (m, 2H), 2.93 (m, 1H), 3.0
1-3.22 (m, 2H), 3.37 (m, 1H),
3.84 (m, 1H), 3.99 (m, 1H), 4.1
2 (m, 1H), 4.38 (m, 1H), 4.92
(M, 1H), 5.09 (s, 2H), 5.56 (d,
J = 7 Hz, 1H), 6.42 (s, 1H), 6.95
~ 7.22 (m, 11H) Example 189 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methoxy-4-phenyl-2-butanone
Production of (Compound No. 447 of Table-1) Melting point: 87 to 92 ° C IR (KBr, cm^-1): 3340, 3285, 173
9,1688,1657 NMR (CDCl₃ , Δ): 0.90 (d, J = 6.2)
Hz, 6H), 1.30 to 1.75 (m, 3H), 2.
90-3.10 (m, 2H), 3.35 (s, 3H),
3.87 (d, J = 18 Hz, 1H), 4.08 (d,
J = 18 Hz, 1H), 4.13 (m, 1H), 4.9
6 (m, 1H), 5.06 (m, 1H), 5.09
(S, 2H), 6.57 (m, 1H), 7.11 (d,
J = 7.4 Hz, 2H), 7.10 to 7.33 (m, 3
H), 7.35 (s, 5H) Example 190 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-dimethylamino-4-phenyl-2-bu
Production of Tanone (Compound No. 465 of Table-1) Melting point: 81-82 ° C IR (KBr, cm^-1): 3330, 3295, 173
0,1683,1653 NMR (CDCl₃ , Δ): 0.75 to 1.0 (m, 6)
H), 1.30 to 1.70 (m, 3H), 2.18
(S, 3H), 2.21 (s, 3H), 2.80-3.
15 (m, 3H), 3.25 (t, J = 19Hz, 1
H), 4.14 (m, 1H), 4.91 (m, 1H),
5.08 (s, 2H), 5.15 to 5.35 (m, 1
H), 6.70 to 6.90 (m, 1H), 7.05
7.18 (m, 2H), 7.18 to 7.30 (m, 3
H), 7.30 to 7.40 (m, 5H) Example 191 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (N-methylfurfurylamino) -4-
Phenyl-2-butanone (Compound No. 479 of Table-1)
Manufacturing of IR (KBr, cm^-1): 3320, 1728, 168
5,1550 NMR (CDCl₃ , Δ): 0.85-1.0 (m, 6
H), 1.25 to 1.80 (m, 3H), 2.25.
(S, 3H), 2.75 to 2.95 (m, 1H), 2.
95-3.15 (m, 2H), 3.28-3.45
(M, 1H), 3.45 to 3.70 (m, 2H), 4.
15 (m, 1H), 4.87 to 5.15 (m, 2H),
5.09 (s, 2H), 6.18 (d, J = 2.8H
z, 1H), 6.29 (dd, J = 3.1 Hz, 1.9)
Hz, 1H), 6.55 to 6.75 (m, 1H), 7.
03 to 7.15 (m, 2H), 7.15 to 7.25
(M, 3H), 7.25 to 7.40 (m, 6H) Example 192 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (4-methyl-1-piperazyl) -4-
Phenyl-2-butanone (Compound No. 488 of Table-1)
Manufacturing of Melting point: 99-100 ° C IR (KBr, cm^-1): 3320, 1733, 169
6,1655 NMR (CDCl₃ , Δ): 0.87 to 1.0 (m, 6
H), 1.30 to 1.70 (m, 3H), 2.27.
(S, 3H), 2.30 to 2.50 (m, 8H), 2.
85-3.10 (m, 3H), 3.10-3.33
(M, 1H), 4.10 (m, 1H), 4.99 (q,
J = 7.4 Hz, 1H), 5.09 (s, 2H), 5.
0 to 5.20 (m, 1H), 6.60 to 6.90 (m,
1H), 7.15 (d, J = 7.0Hz, 2H), 7.
18 to 7.30 (m, 3H), 7.30 to 7.40
(M, 5H) Example 193 3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-4- (4-fluorophenyl) -1-furfurylthio
Preparation of 2-butanone (Compound No. 496 of Table-1) Melting point: 101 ° C IR (KBr, cm^-1): 3300, 1720, 168
0,1650 NMR (CDCl₃ , Δ): 0.82-0.99 (m,
6H), 1.23 to 1.75 (m, 3H), 2.82 to
3.02 (m, 1H), 3.05 to 3.25 (m, 3
H), 3.65 (s, 2H), 4.05 to 4.18.
(M, 1H), 4.90 to 5.02 (m, 2H), 5.
07 (s, 2H), 6.21 (d, J = 3.0Hz, 1
H), 6.28 (m, 1H), 6.50 to 6.55.
(M, 1H), 6.87 to 7.0 (m, 2H), 7.0
3 to 7.15 (m, 2H), 7.25 to 7.40 (m,
6H) Example 194 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4- (2-chlorophenyl) -1-furfuri
Of ruthio-2-butanone (Compound No. 503 of Table-1)
Manufacturing Melting point: 110 ° C IR (KBr, cm^-1): 3300, 1735, 169
0,1660 NMR (CDCl₃ , Δ): 0.86 (d, J = 6.0)
Hz, 3H), 0.88 (d, J = 6.0Hz, 3
H), 1.21-1.80 (m, 3H), 2.97-
3.12 (m, 1H), 3.19 to 3.38 (m, 1)
H), 3.28 (s, 2H), 3.67 (s, 2H),
4.10 (m, 1H), 4.90 to 5.07 (m, 2
H), 5.09 (d, J = 3.9 Hz, 2H), 6.2
1 (d, J = 2.8 Hz, 1H), 6.30 (m, 1
H), 6.63 (m, 1H), 7.08 to 7.20.
(M, 5H), 7.30 to 7.51 (m, 5H) Example 195 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4- (4-chlorophenyl) -1-methylthio
Preparation of o-2-butanone (Compound No. 506 of Table-1) Melting point: 119 to 121 ° C IR (KBr, cm^-1): 3320, 3280, 170
3,1685, 1658 NMR (CDCl₃ , Δ): 0.80 to 1.0 (m, 6)
H), 1.30 to 1.65 (m, 3H), 1.99
(S, 3H), 2.93 (dd, J = 7.0 Hz, 15
Hz, 1H), 3.05 to 3.35 (m, 3H), 4.
15 (m, 1H), 4.90 to 5.22 (m, 2H),
5.10 (s, 2H), 5.62 (d, J = 7Hz, 1
H), 7.07 (d, J = 8.2 Hz, 2H), 7.2
3 (d, J = 8.2 Hz, 2H), 7.36 (s, 5
H) Example 196 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4- (4-chlorophenyl) -1-furfuri
Of ruthio-4-butanone (Compound No. 508 of Table-1)
Manufacturing IR (KBr, cm^-1): 3300, 3270, 170
5,1685,1645 NMR (CDCl₃ , Δ): 0.82 to 0.95 (m,
6H), 1.30 to 1.66 (m, 3H), 2.93.
(M, 1H), 3.05 to 3.15 (m, 3H), 3.
64 (s, 2H), 4.10 (m, 1H), 4.90-
5.05 (m, 2H), 5.10 (s, 2H), 6.1
9 (m, 1H), 6.30 (m, 1H), 6.57
(M, 1H), 7.06 (d, J = 8.2Hz, 2
H), 7.18 to 7.30 (m, 3H), 7.30 to
7.40 (m, 5H) Example 197 (s) -4- (4-chloro)
Phenyl) -1-furfurylthio-3-((s) -4-
Methyl-2-phenoxyacetylaminovalerylami
No) -2-butanone (Compound No. 511 of Table-1)
Construction IR (KBr, cm^-1): 3280, 1720, 164
5 NMR (CDCl₃ , Δ): 0.80 to 0.95 (m,
6H), 1.38 to 1.70 (m, 3H), 2.90.
(Dd, J = 7.3 Hz, 14 Hz, 1 H), 3.10
~ 3.23 (m, 3H), 3.66 (s, 2H), 4.
35-4.53 (m, 3H), 4.97 (m, 1H),
6.20 (m, 1H), 6.30 (m, 1H), 6.6
3 (d, J = 7Hz, 1H), 6.73 (d, J = 8H
z, 1H), 7.88 to 7.95 (m, 2H), 7.0
~ 7.15 (m, 3H), 7.20 ~ 7.40 (m, 5
H) Example 198 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4- (4-methoxyphenyl) -1-methyl
Preparation of thio-2-butanone (Compound No. 516 of Table-1)
Construction Melting point: 100-101 ° C IR (KBr, cm^-1): 3340, 1730, 170
5,1683,1662 NMR (CDCl₃ , Δ): 0.89 (d, J = 6.0)
Hz, 6H), 1.30 to 1.75 (m, 3H), 1.
99 (s, 3H), 2.85 to 3.25 (m, 4H),
3.75 (s, 3H), 4.12 (m, 1H), 4.9
5 to 5.20 (m, 2H), 5.10 (s, 2H),
6.54 (d, J = 7 Hz, 1H), 6.78 (d, J
= 8.6 Hz, 2H), 7.06 (d, J = 8.6H
z, 2H), 7.35 (s, 5H) Example 199 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4- (4-hydroxyphenyl) -1-methyl
Of ruthio-2-butanone (Compound No. 520 of Table-1)
Manufacturing Melting point: 108-111 ° C IR (KBr, cm^-1): 3440, 3340, 172
5,1683,1658 NMR (CDCl₃ , Δ): 0.89 (d, J = 5.9)
Hz, 6H), 1.30 to 1.75 (m, 3H), 1.
99 (s, 3H), 2.89 (m, 1H), 2.99-
3.30 (m, 3H), 4.14 (m, 1H), 4.9
5 to 5.10 (m, 2H), 5.10 (s, 2H),
5.72 (s, 1H), 6.58 to 6.80 (m, 1
H), 6.70 (d, J = 8.2 Hz, 2H), 6.9.
8 (d, J = 8.2 Hz, 2H), 7.35 (s, 5
H) Example 200 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylthio-4- (2-thienyl) -2
-Production of butanone (Compound No. 527 of Table-1) Melting point: 93-97 ° C IR (KBr, cm^-1): 3340, 3290, 172
8,1688,1655 NMR (CDCl₃ , Δ): 0.92 (d, J = 6.2)
Hz, 6H), 1.35 to 1.75 (m, 3H), 2.
0 (s, 3H), 3.14 (d, J = 15Hz, 1
H), 3.23-3.50 (m, 3H), 4.18.
(M, 1H), 4.93 to 5.13 (m, 2H), 5.
11 (s, 2H), 6.70 to 6.85 (m, 2H),
6.90 (m, 1H), 7.14 (d, J = 5.1H
z, 1H), 7.35 (s, 5H) Example 201 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-4- (2-thienyl)
Preparation of 2-butanone (Compound No. 529 of Table-1) Melting point: 106-107 ° C IR (KBr, cm^-1): 3350, 3300, 173
0,1692,1662 NMR (CDCl₃ , Δ): 0.92 (d, J = 6.0)
Hz, 6H), 1.38 to 1.75 (m, 3H), 3.
12-3.43 (m, 4H), 3.64 (s, 2H),
4.18 (m, 1H), 4.90-5.15 (m, 2)
H), 5.11 (s, 2H), 6.16 (d, J = 3.
1 Hz, 1 H), 6.30 (m, 1 H), 6.67-
6.88 (m, 2H), 6.89 (m, 1H), 7.1
3 (d, J = 5.1 Hz, 1H), 7.30 to 7.40
(M, 6H) Example 202 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylthio-5-phenyl-2-penta
Production of Non (Compound No. 534 of Table-1) Melting point: 119 to 120 ° C IR (KBr, cm^-1): 3320, 1715, 168
5,1645 NMR (CDCl₃ , Δ): 0.95 (d, J = 6.2)
Hz, 6H), 1.40 to 1.75 (m, 3H), 1.
95 (m, 1H), 2.05 (s, 3H), 2.28
(M, 1H), 2.63 (t, J = 7.8Hz, 2
H), 3.17 (d, J = 15 Hz, 1H), 3.33
(D, J = 15 Hz, 1H), 4.18 (m, 1H),
4.86 (m, 1H), 4.99 (d, J = 7Hz, 1
H), 5.12 (s, 2H), 6.58 (d, J = 7H
z, 1H), 7.10 to 7.40 (m, 10H) Example 203 (s) -3-((s) -4
-Methyl-2-phenoxyacetylaminovalerylami
No) -1-methylthio-5-phenyl-2-pentanone
Production of (Compound No. 536 of Table-1) IR (KBr, cm^-1): 3260, 1720, 165
0 NMR (CDCl₃ , Δ): 0.85 to 1.02 (m,
6H), 1.50 to 1.80 (m, 3H), 1.93
(M, 1H), 2.06 (s, 3H), 2.30 (m,
1H), 2.62 (t, J = 7.6Hz, 2H), 3.
17 (d, J = 14 Hz, 1H), 3.32 (d, J =
14Hz, 1H), 4.50 (m, 1H), 4.54
(S, 2H), 4.88 (m, 1H), 6.63 (d,
J = 7 Hz, 1H), 6.82 to 7.10 (m, 4
H), 7.10 to 7.40 (m, 7H) Example 204 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-5-phenyl-2-pe
Production of Ntanone (Compound No. 540 of Table-1) Melting point: 73-77 ° C IR (KBr, cm^-1): 3340, 1704, 168
0,1658 NMR (CDCl₃ , Δ): 0.94 (d, J = 5.9)
Hz, 6H), 1.40 to 1.75 (m, 3H), 1.
91 (m, 1H), 2.21 (m, 1H), 2.61
(T, J = 7.5 Hz, 2H), 3.15 to 3.35.
(M, 2H), 3.70 (s, 2H), 4.16 (m,
1H), 4.78 (m, 1H), 5.02 (d, J =
7.5 Hz, 1H), 5.12 (s, 2H), 6.20
(D, J = 2.9 Hz, 1H), 6.28 (m, 1
H), 6.59 (d, J = 7 Hz, 1H), 7.08-
7.45 (m, 11H) Example 205 (s) -3-((R) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-5-phenyl-2-pe
Production of Ntanone (Compound No. 540 of Table-1) Melting point: 107 ° C IR (KBr, cm^-1): 3320, 1725, 169
0,1645 NMR (CDCl₃ , Δ): 0.95 (d, J = 6.1)
Hz, 6H), 1.35 to 2.0 (m, 4H), 2.2
5 (m, 1H), 2.50 to 2.65 (m, 2H),
3.20 (d, J = 15 Hz, 1H), 3.28 (d,
J = 15 Hz, 1H), 3.70 (s, 2H), 4.1
7 (m, 1H), 4.78 (m, 1H), 5.10
(M, 1H), 5.12 (d, J = 1.8Hz, 2
H), 6.20 (d, J = 2.1 Hz, 1H), 6.2
7 (m, 1H), 6.63 (m, 1H), 7.10
7.40 (m, 11H) Example 206 (s) -1-furfurylchi
O-3-((s) -4-methyl-2-phenoxyacetyl
Luminovalerylamino) -5-phenyl-2-penta
Production of Non (Compound No. 543 of Table-1) IR (KBr, cm^-1): 3270, 1720, 165
5 NMR (CDCl₃ , Δ): 0.90 to 0.95 (m,
6H), 1.48 to 1.80 (m, 3H), 1.90.
(M, 1H), 2.22 (m, 1H), 2.60 (t,
J = 7.8Hz, 2H), 3.22 (d, J = 15H
z, 1H), 3.30 (d, J = 15Hz, 1H),
3.71 (s, 2H), 4.50 (m, 1H), 4.5
4 (s, 2H), 4.78 (m, 1H), 6.21
(M, 1H), 6.28 (m, 1H), 6.62 (d,
J = 8Hz, 1H), 6.86 (d, J = 8Hz, 1
H), 6.90-6.98 (m, 1H), 7.03
(T, J = 7.3 Hz, 1H), 7.06 to 7.36
(M, 9H) Example 207 3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-1-Methylthio-4- (1-naphthyl) -2-butano
(Compound No. 547 of Table-1) Melting point: 77-80 ° C IR (KBr, cm^-1): 3340, 1700, 168
5,1665 NMR (CDCl₃ , Δ): 0.78 to 0.90 (m,
6H), 1.20 to 1.65 (m, 3H), 1.92
(S, 1.5H), 1.95 (s, 1.5H), 2.9
3 (t, J = 14 Hz, 2H), 3.52 (d, J =
7.1 Hz, 2H), 4.07 (m, 1H), 4.92
(M, 1H), 5.09 (s, 2H), 5.18 (m,
1H), 6.55 to 6.65 (m, 1H), 7.20 to
7.45 (m, 7H), 7.50 to 7.62 (m, 2
H), 7.76 (dd, J = 2.7 Hz, 7.8 Hz,
1H), 7.86 (d, J = 8.0 Hz, 1H), 8.
20 (d, J = 7.8Hz, 1H) Example 208 3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-1-furfurylthio-4- (1-naphthyl) -2-bu
Production of Tanone (Compound No. 550 of Table-1) Melting point: 71-74 ° C IR (KBr, cm^-1): 3330, 1730, 169
0,1650 NMR (CDCl₃ , Δ): 0.78 to 0.90 (m,
6H), 1.25 to 1.60 (m, 3H), 2.90 to
3.05 (m, 2H), 3.49 (d, J = 7.1H
z, 2H), 3.57 (d, J = 6.3Hz, 2H),
4.08 (m, 1H), 4.88 (m, 1H), 5.0
8 (s, 2H), 5.11 (m, 1H), 6.12
(M, 1H), 6.25 (m, 1H), 6.57 (d,
J = 7 Hz, 0.5 H), 6.66 (d, J = 7 Hz,
0.5H), 7.20 to 7.40 (m, 8H), 7.4
2 to 7.62 (m, 2H), 7.75 (dd, J = 3.
1 Hz, 8.2 Hz, 1H), 7.85 (d, J = 8.
0Hz, 1H), 8.17 (d, J = 8.0Hz, 1
H) Example 209 1-furfurylthio-3-
((S) -4-methyl-2-phenoxyacetylamino
Valerylamino) -4- (1-naphthyl) -2-butano
(Compound No. 555 of Table-1) IR (KBr, cm^-1): 3280, 1650 NMR (CDCl₃ , Δ): 0.72 to 0.92 (m,
6H), 1.20 to 1.70 (m, 3H), 2.90 to
3.05 (m, 2H), 3.40 to 3.60 (m, 2
H), 3.60 (s, 2H), 4.41 (m, 1H),
4.45 (s, 2H), 5.11 (m, 1H), 6.1
4 (m, 1H), 6.25 (m, 1H), 6.65
7.12 (m, 5H), 7.20 to 7.42 (m, 5)
H), 7.42 to 7.65 (m, 2H), 7.70 to
7.90 (m, 2H), 8.13 (t, J = 8.3H
z, 1H) Example 210 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-methylthio-4- (2-naphthyl) -2
-Production of butanone (Compound No. 559 of Table-1) Melting point: 101 to 103 ° C IR (KBr, cm^-1): 3340, 1730, 169
0,1650 NMR (CDCl₃ , Δ): 0.65 to 0.76 (m,
2.4H), 0.83 (d, J = 5.7Hz, 3.6
H), 1.25 to 1.63 (m, 3H), 1.97.
(S, 1.8H), 1.99 (s, 1.2H), 3.0
5 to 3.40 (m, 4H), 4.08 (m, 1H),
4.94 to 5.07 (m, 3H), 5.16 (q, J =
7.0 Hz, 1 H, 6.52 (d, J = 7 Hz, 0.
4H), 6.68 (d, J = 7Hz, 0.6H), 7.
25 to 7.40 (m, 6H), 7.40 to 7.50
(M, 2H), 7.60 (s, 1H), 7.70 to 7.
85 (m, 3H) Example 211 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1-furfurylthio-4- (2-naphthyl)
Preparation of 2-butanone (Compound No. 563 of Table-1) Melting point: 103-104 ° C IR (KBr, cm^-1): 3330, 3300, 171
0,1690,1650 NMR (CDCl₃ , Δ): 0.70 to 0.80 (m,
1.8H), 0.84 (d, J = 5.7Hz, 4.2)
H), 1.20 to 1.60 (m, 3H), 3.10
3.40 (m, 4H), 3.61 (s, 1.4H),
3.64 (s, 0.6H), 4.10 (m, 1H),
4.90 to 5.15 (m, 4H), 6.14 (m, 1
H), 6.26 (m, 1H), 6.52 (d, J = 7H
z, 0.3H), 6.64 (d, J = 7Hz, 0.7
H), 7.26 to 7.40 (m, 7H), 7.40 to
7.50 (m, 2H), 7.59 (m, 1H), 7.7
6 to 7.84 (m, 3H) Example 212 (s) -1-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -3-methylthio-1-phenyl-2-propa
Production of Non (Compound No. 565 of Table-1) IR (neat, cm^-1): 3330, 1710, 16
Fifty NMR (CDCl₃ , Δ): 0.80 to 1.0 (m, 6)
H), 1.20 to 1.75 (m, 3H), 2.00
(S, 3H), 3.08 (dd, J = 3.4 Hz, 14
Hz, 1H), 3.25 (dd, J = 3.8Hz, 14
Hz, 1H), 4.25 (m, 1H), 5.09 (s,
1H), 5.13 (s, 1H), 5.92 (d, J =
6.3 Hz, 1H), 7.17 (m, 1H), 7.25
~ 7.45 (m, 10H) Example 213 (s) -4-benzyloxy
-3-((s) -2-benzyloxycarbonylamino-
4-Methylvalerylamino) -1-methylthio-2-bu
Production of Tanone (Compound No. 571 of Table-1) Melting point: 58 to 70 ° C IR (KBr, cm^-1): 3340, 1723, 168
8,1650 NMR (CDCl₃ , Δ): 0.85 to 1.05 (m,
6H), 1.40 to 1.80 (m, 3H), 2.02
(S, 3H), 3.22 (d, J = 15Hz, 1H),
3.35 (d, J = 15 Hz, 1H), 3.65 (m,
1H), 3.93 (m, 1H), 4.23 (m, 1)
H), 4.43 (d, J = 13 Hz, 1H), 4.53
(D, J = 13 Hz, 1H), 5.0 (m, 1H),
5.11 (s, 2H), 5.15 (m, 1H), 6.9
0 (m, 1H), 7.20 to 7.45 (m, 10H) Example 214 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1,5-bis (methylthio) -2-pentano
(Compound No. 584 of Table-1) Melting point: 61 to 67 ° C IR (KBr, cm^-1): 3320, 1715, 168
2,1642 NMR (CDCl₃ , Δ): 0.93 (d, J = 5.4)
Hz, 6H), 1.45 to 2.35 (m, 5H), 2.
06 (s, 3H), 2.07 (s, 3H), 2.49
(T, J = 6.9 Hz, 2H), 3.24 (d, J = 1
4Hz, 1H), 3.36 (d, J = 14Hz, 1
H), 4.23 (m, 1H), 4.93 (m, 1H),
5.11 (s, 2H), 5.35 (m, 1H), 6.9
8 (m, 1H), 7.34 (s, 5H) Example 215 3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-5-furfurylthio-1-methylthio-2-pentano
(Compound No. 588 of Table-1) IR (neat, cm^-1): 3350, 3310, 17
15, 1690, 1660, 1643 NMR (CDCl₃ , Δ): 0.93 (d, J = 5.5)
Hz, 3H), 0.95 (d, J = 5.5Hz, 3
H), 1.45 to 1.93 (m, 4H), 2.05
(S, 3H), 2.13 (m, 1H), 2.50 (t,
J = 6.7 Hz, 2H), 3.14 to 3.42 (m, 2)
H), 3.70 (s, 2H), 4.21 (m, 1H),
4.89 (m, 1H), 5.12 (s, 2H), 5.1
3 (m, 1H), 6.19 (d, J = 2.9 Hz, 1
H), 6.32 (m, 1H), 6.77 (m, 1H),
7.30 to 7.40 (m, 6H) Example 216 (s) -4-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -6-furfurylthio-5-oxohexanoic acid
  Production of methyl ester (Compound No. 598 of Table-1) IR (neat, cm^-1): 3330, 1735, 17
15,1660 NMR (CDCl₃ , Δ): 0.93 (d, J = 5.9)
Hz, 6H), 1.42 to 2.50 (m, 7H), 3.
29 (d, J = 15 Hz, 1 H), 3.36 (d, J =
15Hz, 1H), 3.65 (s, 3H), 3.70
(S, 2H), 4.19 (m, 1H), 4.77 (m,
1H), 5.11 (s, 2H), 5.16 (m, 1
H), 6.22 (d, J = 2.4 Hz, 1H), 6.2
8 (m, 1H), 6.90 (m, 1H), 7.25 ~
7.40 (m, 6H) Example 217 (s) -4-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -6-furfurylthio-5-oxohexanoic acid
  Production of (Compound No. 600 in Table-1) IR (neat, cm^-1): 3420, 1710, 16
Fifty NMR (CDCl₃ , Δ): 0.91 (d, J = 5.0
Hz, 6H), 1.40 to 2.75 (m, 7H), 3.
31 (s, 2H), 3.68 (s, 2H), 4.22
(M, 1H), 4.78 (m, 1H), 5.09 (s,
2H), 5.43 (m, 1H), 6.19 (d, J =
2.1 Hz, 1H), 6.26 (m, 1H), 6.91
(M, 1H), 7.13 to 7.35 (m, 7H) Example 218 1-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-3-furfurylthio-1-propoxy-2-propano
(Compound No. 604 of Table-1) IR (neat, cm^-1): 3300, 1710, 16
60 NMR (CDCl₃ , Δ): 0.89 (t, J = 7.5)
Hz, 3H), 0.95 (d, J = 5.9Hz, 6
H), 1.40 to 1.80 (m, 5H), 3.37.
(D, J = 15 Hz, 1H), 3.50 (d, J = 15
Hz, 1H), 3.50 to 3.67 (m, 2H), 3.
68 (s, 2H), 4.25 (m, 1H), 5.12
(S, 2H), 5.14 (m, 1H), 5.76 (m,
1H), 6.20 (d, J = 2.5Hz, 1H), 6.
28 (m, 1H), 6.88 (d, J = 9Hz, 0.7
H), 6.97 (d, J = 9 Hz, 0.3H), 7.3
0 to 7.40 (m, 6H) Example 219 3-((s) -2-benzi
Roxycarbonylamino-4-methylvalerylamino)
-4-Phenyl-1-phenylthio-3-butene-2-
Production of ON (Compound No. 610 of Table-1) Melting point: 142-143 ° C IR (KBr, cm^-1): 3385, 1692, 165
0 NMR (CDCl₃ , Δ): 0.93 (d, J = 5.2)
Hz, 3H), 0.96 (d, J = 6.1Hz, 3
H), 1.52 (m, 1H), 1.70 (m, 2H),
3.98 (s, 2H), 4.38 (m, 1H), 5.0
5 (d, J = 6.5 Hz, 1H), 5.13 (s, 2
H), 7.09 (s, 1H), 7.20 to 7.48.
(M, 15H), 7.88 (s, 1H) Example 220 (s) -1-furfurylchi
O-3-[(s) -2- {3- (2-furyl) acrylo
Ilamino} -4-methylvalerylamino] -2-hep
Production of tan (Compound No. 645 of Table-1) IR (KBr, cm^-1): 3272, 1715, 165
1,1618 NMR (CDCl₃ , Δ): 0.81 (t, J = 6.7)
Hz, 3H), 0.92 (d, J = 5.6Hz, 6
H), 1.13 to 1.41 (m, 4H), 1.45
1.79 (m, 4H), 1.85 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.36 (d, J = 1
5Hz, 1H), 3.72 (s, 2H), 4.62 ~
4.83 (m, 2H), 6.18 to 6.60 (m, 6
H), 7.06 (d, J = 7.7 Hz, 1H), 7.2
8 to 7.51 (m, 3H) Example 221 (s) -3-((s) -1
-Benzyloxycarbonyl-2-pyrrolidinylamino)
-1-furfurylthio-2-heptanone (compounds in Table-1
Product No. 669) IR (neat, cm^-1): 3320, 1720, 16
80 NMR (CDCl₃ , Δ): 0.86 (t, J = 6.7)
Hz, 3H), 1.10 to 1.39 (m, 4H), 1.
55 (m, 1H), 1.75 to 2.10 (m, 4H),
2.21 (m, 1H), 3.03 to 3.38 (m, 2)
H), 3.38 to 3.63 (m, 2H), 3.63 to
3.78 (m, 2H), 4.36 (m, 1H), 4.6
7 (m, 1H), 5.18 (s, 2H), 6.22
(M, 1H), 6.29 (m, 1H), 6.58 (m,
1H), 7.22 to 7.45 (m, 6H) Example 222 (s) -3-((s) -1
-Benzyloxycarbonyl-2-pyrrolidinyl carbonate
Lumino) -1-methylthio-4-phenyl-2-buta
Production of Non (Compound No. 673 of Table-1) IR (neat, cm^-1): 3330, 1705, 16
80 NMR (CDCl₃ , Δ): 1.40 to 2.05 (m,
4H), 1.97 (s, 3H), 2.85 to 3.60.
(M, 6H), 4.31 (m, 1H), 5.02 (m,
1H), 5.15 (s, 2H), 7.12 (d, J =
7.5 Hz, 2H), 7.15 to 7.45 (m, 8H) Example 223 (s) -3-((s) -2
-Benzyloxycarbonyl-3-perhydroisoquinoli
L-carbonylamino) -1-furfurylthio-4-phen
Preparation of Nil-2-butanone (Compound No. 683 of Table-1)
Construction IR (neat, cm^-1): 3350, 1690 NMR (CDCl₃ , Δ): 1.15 to 1.90 (m,
12H), 2.80 to 3.25 (m, 6H), 3.60.
Up to 3.70 (m, 2H), 4.70 to 5.25 (m, 4)
H), 6.20 (m, 1H), 6.29 (m, 1H),
6.52 (m, 1H), 7.0 to 7.45 (m, 11
H) Example 224 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-methylphene)
(Noxyacetylamino) valerylamino] -2-hepta
Production of Non (Compound No. 98 of Table-1) Melting point 93 ° C IR (KBr, cm^-1): 3279, 1707, 166
0,1649 NMR (CDCl₃, Δ): 0.86 (t, J = 6.9)
Hz, 3H), 0.92 (d, J = 4.2Hz, 6
H), 1.13 to 1.41 (m, 4H), 1.44 to
1.81 (m, 4H), 1.89 (m, 1H), 2.2
9 (s, 3H), 3.27 (d, J = 15Hz, 1
H), 3.34 (d, J = 15 Hz, 1H), 3.73
(S, 2H), 4.48 (s, 2H), 4.59 (m,
1H), 4.75 (m, 1H), 6.22 (d, J =
2.9 Hz, 1H), 6.29 (m, 1H), 6.78
˜6.90 (m, 3H), 6.97 (d, J = 8.4H
z, 1H), 7.10 (d, J = 8.4Hz, 2H),
7.35 (m, 1H) Example 225 (s) -3-[(s) -2
-(2,4-Dimethoxybenzoylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 154 of Table-1) IR (neat, cm^-1): 3383, 3285, 17
17,1660,1635 NMR (CDCl₃, Δ): 0.78 (t, J = 6.6
Hz, 3H), 0.96 (d, J = 6.2Hz, 3
H), 0.98 (d, J = 6.4 Hz, 3H), 1.1
3 to 1.37 (m, 5H), 1.42 to 1.97 (m,
4H), 3.27 (d, J = 15Hz, 1H), 3.3
7 (d, J = 15 Hz, 1 H), 3.72 (s, 2
H), 3.86 (s, 3H), 3.95 (s, 3H),
4.62 to 4.79 (m, 2H), 6.22 (m, 1)
H), 6.29 (m, 1H), 6.49 (d, J = 2.
2Hz, 1H), 6.60 (dd, J = 8.8Hz,
2.2 Hz, 1 H), 7.10 (d, J = 7.5 Hz,
1H), 7.35 (m, 1H), 8.05 (d, J =
7.5 Hz, 1 H), 8.14 (d, J = 8.8 Hz,
1H) Example 226 (s) -3-((s) -2
-Cinnamoylamino-4-methylvalerylamino)-
1-furfurylthio-2-heptanone (Compounds of Table-1
No. 163) manufacture IR (KBr, cm^-1): 3272, 1715, 164
9,1618 NMR (CDCl₃, Δ): 0.82 (t, J = 6.9)
Hz, 3H), 0.96 (d, J = 5.5Hz, 6
H), 1.15 to 1.43 (m, 4H), 1.45
1.79 (m, 4H), 1.83 (m, 1H), 3.2
9 (m, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.62 ~
4.82 (m, 2H), 6.21 (d, J = 3.2H
z, 1H), 6.29 (m, 1H), 6.46 (d, J
= 16 Hz, 1 H), 6.54 (d, J = 8.4 Hz,
1H), 7.05 (d, J = 7.6Hz, 1H), 7.
28 to 7.40 (m, 4H), 7.41 to 7.56
(M, 2H), 7.63 (d, J = 16Hz, 1H) Example 227 (s) -1-furfurylchi
O-3-((s) -4-methyl-2-phenylsulfoni
Ruaminovalerylamino) -2-heptanone (Table 1
Production of compound number 192) Melting point 110-112 ° C IR (KBr, cm^-1): 3366, 3150, 170
9,1655 NMR (CDCl₃, Δ): 0.70 (d, J = 7.9)
Hz, 3H), 0.78-0.95 (m, 6H), 1.
05 to 1.20 (m, 2H), 1.20 to 1.38
(M, 2H), 1.39 to 1.65 (m, 4H), 1.
76 (m, 1H), 3.26 (d, J = 15Hz, 1
H), 3.30 (d, J = 15 Hz, 1H), 3.70.
(S, 2H), 3.75 (m, 1H), 4.61 (m,
1H), 5.48 (d, J = 7.8Hz, 1H), 6.
21 (d, J = 2.8 Hz, 1 H), 6.29 (m, 1
H), 6.60 (d, J = 7.7 Hz, 1H), 7.3
5 (m, 1H), 7.43 to 7.62 (m, 3H),
7.87 (dd, J = 7.9Hz, 1.1Hz, 2H) Example 228 (s) -3-[(s) -2
-(2,4-dimethoxycinnamoylamino) -4-me
Cylvalerylamino] -1-furfurylthio-4-phen
Production of Nil-2-butanone (Compound No. 337 of Table-1)
Construction Melting point 145-147 ° C IR (KBr, cm^-1): 3271, 1728, 164
5,1607 NMR (CDCl₃, Δ): 0.91 (d, J = 5.9)
Hz, 3H), 0.93 (d, J = 6.1Hz, 3
H), 1.45 to 1.78 (m, 3H), 2.94 (d
d, J = 14 Hz, 7.7 Hz, 1H), 3.12 (d
d, J = 14 Hz, 7.7 Hz, 1H), 3.16
(D, J = 15 Hz, 1H), 3.21 (d, J = 15
Hz, 1H), 3.64 (s, 2H), 3.84 (s,
3H), 3.87 (s, 3H), 4.57 (m, 1
H), 4.96 (m, 1H), 5.84 (d, J = 8.
0Hz, 1H), 6.18 (d, J = 3.2Hz, 1
H), 6.29 (dd, J = 3.2 Hz, 1.9 Hz,
1H), 6.41 (d, J = 16Hz, 1H), 6.4
6 to 6.53 (m, 2H), 6.96 (d, J = 7.6)
Hz, 1H), 7.11 to 7.31 (m, 5H), 7.
34 (m, 1H), 7.39 (d, J = 8.4 Hz, 1
H), 7.79 (d, J = 16Hz, 1H) Example 229 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-methoxyphenyl)
Enoxyacetylamino) valerylamino] -4-phen
Preparation of Nil-2-butanone (Compound No. 363 of Table-1)
Construction Melting point 94-97 ° C IR (KBr, cm^-1): 3437, 3291, 172
6,1657 NMR (CDCl₃, Δ): 0.88 (d, J = 6.2)
Hz, 3H), 0.89 (d, J = 6.1Hz, 3
H), 1.41 to 1.75 (m, 3H), 2.95 (d
d, J = 14 Hz, 7.6 Hz, 1H), 3.14 (d
d, J = 14 Hz, 7.6 Hz, 1H), 3.16
(D, J = 15 Hz, 1H), 3.21 (d, J = 15
Hz, 1H), 3.65 (s, 2H), 3.77 (s,
3H), 4.34 (d, J = 15Hz, 1H), 4.4
4 (d, J = 15 Hz, 1H), 4.46 (m, 1
H), 4.99 (m, 1H), 6.20 (d, J = 3.
3 Hz, 1 H), 6.29 (dd, J = 3.3 Hz,
1.9 Hz, 1 H), 6.24 (d, J = 7.7 Hz,
1H), 6.74 (d, J = 8.2Hz, 1H), 6.
84 (s, 4H), 7.09 to 7.28 (m, 5H),
7.35 (dd, J = 1.9Hz, 0.9Hz, 1H) Example 230 (s) -3-[(s) -2
-(2-Fluorobenzoylamino) -4-methylvale
Rylamino) -1-furfurylthio-4-phenyl-2
-Production of butanone (Compound No. 337 of Table-1) Melting point 116 ° C IR (KBr, cm^-1): 3293, 1725, 163
8,1615 NMR (CDCl₃, Δ): 0.92 (d, J = 5.6)
Hz, 3H), 0.95 (d, J = 5.7Hz, 3
H), 1.45 to 1.80 (m, 3H), 2.96 (d
d, J = 14 Hz, 7.7 Hz, 1H), 3.15 (d
d, J = 14 Hz, 7.7 Hz, 1H), 3.17
(D, J = 15 Hz, 1H), 3.23 (d, J = 15
Hz, 1H), 3.65 (s, 2H), 4.62 (m,
1H), 5.01 (td, J = 7.5Hz, 6.5H
z, 1H), 6.19 (d, J = 3.2Hz, 1H),
3.29 (m, 1H), 6.75 to 6.92 (m, 2)
H), 7.08 to 7.39 (m, 8H), 7.52
(M, 1H), 8.06 (td, J = 7.9 Hz, 1.
9Hz, 1H) Example 231 (s) -1- (2-benzi)
Roxycarbonylamino-4-methylvalerylamino)
-1- (3-pyridylmethylthioacetyl) cyclopro
Preparation of Penone (Compound No. 639 of Table-1) IR (neat, cm^-1): 3326, 1713, 16
80 NMR (CDCl₃, Δ): 0.91 (d, J = 5.8)
Hz, 3H), 0.94 (d, J = 6.1Hz, 3
H), 1.03 to 1.40 (m, 4H), 1.41
1.83 (m, 6H), 1.83 to 2.07 (m, 3
H), 3.24 (s, 2H), 3.71 (s, 2H),
4.12 (m, 1H), 5.05 (d, J = 12Hz,
1H), 5.15 (d, J = 12 Hz, 1H), 5.3
3 (d, J = 5.8 Hz, 1H), 6.73 (s, 1
H), 7.22 (m, 1H), 7.29 to 7.40.
(M, 5H), 7.68 (dd, J = 7.8Hz, 4.
1Hz, 1H), 8.46 (dd, J = 4.8Hz,
1.5Hz, 1H) 8.52 (s, 1H) Example 232 (RS) -3-((s)-
2-benzyloxycarbonylamino-4-methylvaleri
Ruamino) -1- (3-furylmethylthio) -5-methyl
Preparation of le-2-hexanone (Compound No. 699 of Table-1)
Construction IR (neat, cm^-1): 3310, 1705, 16
55 NMR (CDCl₃, Δ): 0.83 to 1.13 (m,
12H), 1.37 to 2.05 (m, 6H), 3.12.
~ 3.35 (m, 2H), 3.52 (s, 2H), 4.
20 (m, 1H), 4.79 (m, 1H), 5.11
(S, 2H), 5.16 (m, 1H), 6.38 (m,
1H), 6.45 to 6.63 (m, 1H), 7.23 to
7.48 (m, 7H) Example 233 (RS) -1- (3-free)
Rumethylthio) -5-methyl-3-((s) -4-methyl
Lu-2-phenoxyacetylaminovalerylamino)-
Preparation of 2-hexanone (Compound No. 701 of Table-1) IR (neat, cm^-1): 3290, 1705, 16
51,1599 NMR (CDCl₃, Δ): 0.82 to 1.02 (m,
12H), 1.40 to 1.82 (m, 6H), 3.12
~ 3.32 (m, 2H), 3.51 (s, 1H), 3.
54 (s, 1H), 4.45 to 4.63 (m, 3H),
4.78 (m, 1H), 6.37 (d, J = 1.3H
z, 0.5H), 6.39 (d, J = 0.6Hz, 0.
5H), 6.48 (d, J = 7.8Hz, 0.5H),
6.62 (d, J = 7.6Hz, 0.5H), 6.86
.About.6.98 (m, 3H), 7.04'm, 1H), 7.
25 to 7.39 (m, 4H) Example 234 (s) -1- (3-furyl)
Methylthio) -3-[(s) -2- (4-methoxyphen)
Noxyacetylamino) -4-methylvalerylamino]
-5-methyl-2-hexanone (Compound No. 7 in Table-1
03) Production IR (neat, cm^-1): 3293, 1708, 16
51 NMR (CDCl₃, Δ): 0.82 to 1.03 (m,
12H), 1.39 to 1.81 (m, 6H), 3.19.
(D, J = 14 Hz, 1H), 3.29 (d, J = 14
Hz, 1H), 3.54 (s, 2H), 3.77 (s,
3H), 4.46 (s, 2H), 4.55 (m, 1
H), 4.78 (m, 1H), 6.39 (m, 1H),
7.61 (d, J = 8.2 Hz, 1H), 6.86
(S, 4H), 6.93 (d, J = 7.8Hz, 1
H), 7.36 to 7.42 (m, 2H) Example 235 (s) -3-[(s) -2
-(2,4-dimethoxycinnamoylamino) -4-me
Cylvalerylamino] -1- (3-furylmethylthio)
-5-methyl-2-hexanone (Compound No. 7 in Table-1
06) production IR (neat, cm^-1): 3272, 1715, 16
45,1605 NMR (CDCl₃, Δ): 0.86 (d, J = 5.8)
Hz, 6H), 0.95 (d, J = 5.1Hz, 6
H), 1.40 to 1.83 (m, 6H), 3.22
(D, J = 14 Hz, 1H), 3.30 (d, J = 14
Hz, 1H), 3.53 (s, 2H), 3.81 (s,
6H), 4.67 to 4.82 (m, 2H), 6.30 to
6.58 (m, 5H), 7.18 (m, 1H), 7.3
1 to 7.40 (m, 3H), 7.80 (d, J = 19H
z, 1H) Example 236 (s) -1- (3-furyl)
Methylthio) -5-methyl-2-[(s) -4-methyl
-2- (4-trifluoromethylbenzoylamino) va
Relylamino] -2-hexanone (Compound number in Table-1
709) production Melting point 135-147 ° C IR (KBr, cm^-1): 3299, 1717, 164
0 NMR (CDCl₃, Δ): 0.90 (d, J = 5.8)
Hz, 6H), 0.99 (d, J = 5.7Hz, 6
H), 1.41 to 1.83 (m, 6H), 3.20.
(D, J = 15 Hz, 1H), 3.29 (d, J = 15
Hz, 1H), 3.54 (s, 2H), 4.69 (m,
1H), 4.83 (m, 1H), 6.39 (m, 1
H), 6.46 (d, J = 8.0 Hz, 1H), 6.6
9 (d, J = 8.4 Hz, 1H), 7.37 to 7.41
(M, 2H), 7.71 (d, J = 8.3Hz, 2H)
7.89 (d, J = 8.3Hz, 2H) Example 237 (s) -1-furfuryl
O-3-[(s) -2- (2,6-dimethylphenoxy)
Acetylamino) -4-methylvalerylamino] -2-
Production of heptanone (Compound No. 713 of Table-1) IR (KBr, cm^-1): 3306, 1707, 166
0,1651 NMR (CDCl₃, Δ): 0.88 (t, J = 7.0)
Hz, 3H), 0.97 to 1.07 (m, 6H), 1.
19 to 1.41 (m, 4H), 1.45 to 1.83
(M, 4H), 1.90 (m, 1H), 2.26 (s,
6H), 3.28 (d, J = 15Hz, 1H), 3.3
6 (d, J = 15 Hz, 1 H), 3.72 (s, 2
H), 4.32 (s, 2H), 4.62 (m, 1H),
4.80 (m, 1H), 6.22 (d, J = 3.0H
z, 1H), 6.30 (m, 1H), 6.71 (d, J
= 7.5 Hz, 1H), 6.92 to 7.07 (m, 3
H), 7.26 (d, J = 7.9 Hz, 1H), 7.3
6 (m, 1H) Example 238 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2-trifluor
Romethylphenoxyacetylamino) valerylamino]
Preparation of 2-heptanone (Compound No. 715 of Table-1) IR (KBr, cm^-1): 3285, 1721, 167
2,1647 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.93 (d, J = 6.2Hz, 3
H), 0.95 (d, J = 6.1 Hz, 3H), 1.1
5 to 1.40 (m, 4H), 1.44 to 1.81 (m,
4H), 1.92 (m, 1H), 3.26 (d, J = 1)
5Hz, 1H), 3.35 (d, J = 15Hz, 1
H), 3.72 (s, 2H), 4.49 (m, 1H),
4.57 (d, J = 15 Hz, 1H), 4.64 (d,
J = 15 Hz, 1H), 4.75 (m, 1H), 6.2
2 (m, 1H), 6.29 (m, 1H), 6.65
(D, J = 7.7 Hz, 1H), 6.87 to 7.05
(M, 2H), 7.13 (dd, J = 7.6 Hz, 7.
6 Hz, 1H), 7.35 (m, 1H), 7.55 (d
d, J = 7.7 Hz, 7.7 Hz, 1H), 7.63
(D, J = 7.8Hz, 1H) Example 239 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (3-trifluor
Romethylphenoxyacetylamino) valerylamino]
Preparation of 2-heptanone (Compound No. 716 of Table-1) Melting point 95-96 ° C IR (KBr, cm^-1): 3285, 1707, 167
1,1647 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.95 (d, J = 6.0 Hz, 6
H), 1.09 to 1.41 (m, 4H), 1.43 to
1.81 (m, 4H), 1.90 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.55
(S, 2H), 4.63 (m, 1H), 4.76 (m,
1H), 6.22 (d, J = 3.1Hz, 1H), 6.
30 (m, 1H), 6.59 (d, J = 7.2 Hz, 1
H), 6.94 (d, J = 7.2 Hz, 1H), 7.0
4 to 7.23 (m, 2H), 7.35 (m, 1H),
7.36 (m, 1H), 7.45 (dd, J = 8.1H
z, 8.1Hz, 1H) Example 240 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-trifluor
Romethylphenoxyacetylamino) valerylamino]
Preparation of 2-heptanone (Compound No. 717 of Table-1) Melting point 69-70 ° C IR (KBr, cm^-1): 3294, 1705, 164
9,1616 NMR (CDCl₃, Δ): 0.85 (t, J = 7.0)
Hz, 3H), 0.93 (d, J = 6.1 Hz, 6
H), 1.17 to 1.41 (m, 4H), 1.45
1.76 (m, 4H), 1.86 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.34 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.47-
4.62 (m, 3H), 4.78 (m, 1H), 6.2
2 (m, 1H), 6.30 (m, 1H), 6.55
(D, J = 7.7 Hz, 1H), 6.90 (d, J =
8.2Hz, 1H), 7.02 (d, J = 8.6Hz,
2H), 7.36 (m, 1H), 7.59 (d, J =
8.6Hz, 2H) Example 241 (s) -3-[(s) -2
-(2-Fluorocinnamoylamino) -4-methylva
Relylamino] -1-furfurylthio-2-heptanone
Production of (Compound No. 718 of Table-1) Melting point 120 ° C IR (KBr, cm^-1): 3270, 1734, 165
9,1620 NMR (CDCl₃, Δ): 0.83 (t, J = 6.7)
Hz, 3H), 0.96 (d, J = 5.8Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.43 to
1.79 (m, 4H), 1.90 (m, 1H), 3.2
7 (d, J = 15 Hz, 1H), 3.35 (d, J = 1
5Hz, 1H), 3.73 (s, 2H), 4.62 ~
4.82 (m, 2H), 6.21 (d, J = 3.1H
z, 1H), 6.29 (m, 1H), 6.38 (d, J
= 8.4 Hz, 1 H), 6.57 (d, J = 16 Hz,
1H), 6.87 (d, J = 7.5 Hz, 1H), 7.
03 to 7.20 (m, 2H), 7.28 (m, 1H),
7.35 (m, 1H), 7.47 (ddd, J = 7.6)
Hz, 7.6 Hz, 1.7 Hz, 1H), 7.71
(D, J = 16Hz, 1H) Example 242 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-trifluor
Romethylcinnamoylamino) valerylamino] -2-
Production of heptanone (Compound No. 721 of Table-1) Melting point 112 ° C IR (KBr, cm^-1): 3304, 1720, 164
7,1618 NMR (CDCl₃, Δ): 0.82 (t, J = 6.9)
Hz, 3H), 0.96 (d, J = 5.8Hz, 6
H), 1.17 to 1.38 (m, 5H), 1.43 to
1.78 (m, 3H), 1.83 (m, 1H), 3.2
7 (d, J = 14 Hz, 1H), 3.35 (d, J = 1
4Hz, 1H), 3.73 (s, 2H), 4.65
4.82 (m, 2H), 6.22 (d, J = 3.2H
z, 1H), 6.29 (m, 1H), 6.55 (d, J
= 16 Hz, 1 H), 6.87 (d, J = 8.4 Hz,
1H), 7.07 (d, J = 7.6Hz, 1H), 7.
35 (m, 1H), 7.43 to 7.59 (m, 4H),
7.62 (d, J = 16Hz, 1H) Example 243 (s) -3-[(s) -2
-(2,3-Dimethoxybenzoylamino) -4-methyl
Luvalerylamino] -1-furfurylthio-2-hepta
Production of Non (Compound No. 722 of Table-1) IR (neat, cm^-1): 3296, 1715, 16
80,1643 NMR (CDCl₃, Δ): 0.79 (t, J = 6.8)
Hz, 3H), 0.83 to 1.08 (m, 6H), 1.
15-1.40 (m, 5H), 1.43-1.98
(M, 4H), 3.27 (d, J = 15Hz, 1H),
3.36 (d, J = 15Hz, 1H), 3.72 (s,
2H), 3.90 (s, 3H), 3.92 (s, 3)
H), 4.61 to 4.79 (m, 2H), 6.22
(D, J = 3.1 Hz, 1 H), 6.29 (m, 1
H), 6.95 (d, J = 7.5 Hz, 1H), 7.0
6 (dd, J = 8.2 Hz, 1.5 Hz, 1 H), 7.
18 (dd, J = 7.8Hz, 7.7Hz, 1H),
7.35 (m, 1H), 7.67 (dd, J = 7.8H
z, 1.5 Hz, 1H), 8.37 (d, J = 7.7H
z, 1H) Example 244 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (2,4,5-to
Rimethoxybenzoylamino) valerylamino] -2-
Production of heptanone (Compound No. 724 of Table-1) Melting point 80-81 ° C IR (KBr, cm^-1): 3296, 1722, 162
6 NMR (CDCl₃, Δ): 0.79 (t, J = 6.7)
Hz, 3H), 0.96 (d, J = 6.1Hz, 3
H), 0.99 (d, J = 6.3 Hz, 3H), 1.1
4 to 1.39 (m, 5H), 1.45 to 1.98 (m,
4H), 3.27 ((d, J = 15Hz, 1H), 3.
37 (d, J = 15 Hz, 1H), 3.71 (s, 2
H), 3.89 (s, 3H), 3.95 (s, 3H),
3.97 (s, 3H), 4.62 to 4.79 (m, 2
H), 6.21 (m, 1H), 6.28 (m, 1H),
6.53 (s, 1H), 7.01 (d, J = 7.6H
z, 1H), 7.35 (m, 1H), 7.71 (s, 1
H), 8.18 (d, J = 7.4Hz, 1H) Example 245 (s) -3-[(s) -2
-{4- (1,3-dioxolan-2-yl) benzoi
Ruamino} -4-methylvalerylamino] -1-furf
Rilthio-2-heptanone (Compound No. 72 in Table 1
5) Manufacturing Melting point 98-104 ° C IR (KBr, cm^-1): 3296, 1709, 165
8,1633 NMR (CDCl₃, Δ): 0.79 (t, J = 6.7)
Hz, 3H), 0.97 (d, J = 5.4Hz, 6
H), 1.10 to 1.38 (m, 4H), 1.43 to
2.15 (m, 5H), 3.27 (d, J = 15Hz,
1H), 3.36 (d, J = 15Hz, 1H), 3.7
3 (s, 2H), 3.98 to 4.17 (m, 4H),
5.62-4.84 (m, 2H), 5.85 (s, 1
H), 6.21 (m, 1H), 6.29 (m, 1H),
6.75 (d, J = 8.2 Hz, 1H), 6.88
(D, J = 7.6 Hz, 1H), 7.36 (m, 1
H), 7.53 (d, J = 8.3 Hz, 2H), 7.7
9 (d, J = 8.3Hz, 2H) Example 246 (s) -1-furfurylchi
O-3-[(s) -2- (2-methoxycarbonyl) be
Nzoylamino-4-methylvalerylamino] -2-f
Preparation of Ptanone (Compound No. 727 of Table-1) IR (neat, cm^-1): 3356, 3288, 17
17,1660,1647 NMR (CDCl₃, Δ): 0.87 (t, J = 7.0)
Hz, 3H), 0.94 (d, J = 6.0 Hz, 6
H), 1.12 to 1.38 (m, 4H), 1.43 to
1.78 (m, 4H), 1.83 (m, 1H), 3.3
7 (d, J = 15 Hz, 1H), 3.42 (d, J = 1
5Hz, 1H), 3.72 (s, 2H), 3.83
(S, 3H), 4.60 to 4.82 (m, 2H), 6.
09 (d, J = 7.5 Hz, 1H), 6.23 (d, J
= 2.3 Hz, 1H), 6.28 (m, 1H), 6.3
6 (m, 1H), 7.39 to 7.75 (m, 4H),
7.96 (m, 1H) Example 247 (s) -3-[(s) -2
-Tert-butoxycarbonylamino-4-methylva
Lerylamino) -1- (3-furylmethylthio) -2-
Production of heptanone (Compound No. 729 of Table-1) Melting point 56-57 ° C IR (KBr, cm^-1): 3339, 1705, 168
0,1663 NMR (CDCl₃, Δ): 0.88 (t, J = 6.8)
Hz, 3H), 0.93 to 0.96 (m, 6H), 1.
07-1.46 (m, 5H), 1.44 (s, 9H),
1.47 to 1.75 (m, 3H), 1.75 to 1.97
(M, 1H), 3.17 (d, J = 15Hz, 1H),
3.27 (d, J = 15Hz, 1H), 3.53 (s,
2H), 4.10 (m, 1H), 4.78 (m, 1)
H), 4.88 (d, J = 7.9 Hz, 1H), 6.3
8 (m, 1H), 6.72 (d, J = 7.7 Hz, 1
H), 7.34 to 7.42 (m, 2H) Example 248 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (3-furylmethylthio) -2-hepta
Production of Non (Compound No. 732 of Table-1) Melting point 67-68 ° C IR (KBr, cm^-1): 3302, 1732, 169
1,1653 NMR (CDCl₃, Δ): 0.87 (t, J = 7.1)
Hz, 3H), 0.94 (d, J = 5.9Hz, 6
H), 1.14 to 1.41 (m, 4H), 1.43 to
1.78 (m, 4H), 1.84 (m, 1H), 3.1
6 (d, J = 15 Hz, 1H), 3.27 (d, J = 1
5Hz, 1H), 3.52 (s, 2H), 4.21
(M, 1H), 4.79 (m, 1H), 5.11 (s,
2H), 5.14 (d, J = 7.4Hz, 1H), 6.
38 (m, 1H), 6.57 (d, J = 7.7 Hz, 1
H), 7.35 to 7.42 (m, 7H) Example 249 (s) -1- (3-furyl
Methylthio) -3-[(s) -2- (2-methoxyben
Diroxycarbonylamino) -4-methylvalerylami
No] -2-heptanone (Compound No. 736 of Table-1)
Manufacturing Melting point 81-82 ° C IR (KBr, cm^-1): 3316, 1717, 168
5,1641,1608 NMR (CDCl₃, Δ): 0.87 (t, J = 7.0)
Hz, 3H), 0.94 (d, J = 6.1Hz, 6
H), 1.10 to 1.40 (m, 4H), 1.41
1.79 (m, 4H), 1.83 (m, 1H), 3.1
6 (d, J = 15 Hz, 1H), 3.27 (d, J = 1
5Hz, 1H), 3.52 (s, 2H), 3.84
(S, 3H), 4.19 (m, 1H), 4.75 (m,
1H), 5.11 (d, J = 7.1Hz, 1H), 5.
18 (s, 2H), 6.38 (m, 1H), 6.58
(D, J = 7.7 Hz, 1H), 6.92 to 6.99
(M, 2H), 7.27 to 7.38 (m, 2H), 7.
38-7.42 (m, 2H) Example 250 (s) -1- (3-furyl)
Methylthio) -3-[(s) -2- (3-methoxyben
Diroxycarbonylamino) -4-methylvalerylami
No] -2-heptanone (Compound No. 737 of Table-1)
Manufacturing IR (KBr, cm^-1): 3306, 1709, 165
7 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 2H), 0.94 (d, J = 6.0Hz, 6
H), 1.11 to 1.39 (m, 4H), 1.42
1.79 (m, 4H), 1.83 (m, 1H), 3.1
7 (d, J = 15 Hz, 1H), 3.27 (d, J = 1
5Hz, 1H), 3.49 (s, 2H), 3.80
(S, 3H), 4.21 (m, 1H), 4.77 (m,
1H), 5.08 (s, 2H), 5.25 (d, J =
8.1Hz, 1H), 6.37 (m, 1H), 6.63
(D, J = 7.6 Hz, 1H), 6.81 to 6.98
(M, 3H), 7.21 to 7.37 (m, 1H), 7.
36 to 7.42 (m, 2H) Example 251 (s) -1- (3-furyl)
Methylthio) -3-[(s) -2- (4-methoxyben)
Diroxycarbonylamino) -4-methylvalerylami
No] -2-heptanone (Compound No. 738 of Table-1)
Manufacturing Melting point 70-71 ° C IR (KBr, cm^-1): 3298, 1701, 168
2,1649,1614 NMR (CDCl₃, Δ): 0.87 (t, J = 8.9)
Hz, 3H), 0.93 (d, J = 5.0Hz, 6
H), 1.07 to 1.39 (m, 4H), 1.41
1.78 (m, 4H), 1.87 (m, 1H), 3.1
6 (d, J = 15 Hz, 1H), 3.27 (d, J = 1
5Hz, 1H), 3.52 (s, 2H), 3.80
(S, 3H), 4.18 (m, 1H), 4.76 (m,
1H), 5.04 (s, 2H), 5.10 (d, J =
7.9 Hz, 1H), 6.37 (m, 1H), 6.57
(D, J = 7.5 Hz, 1H), 6.87 (d, J =
8.6 Hz, 2 H), 7.28 (d, J = 8.6 Hz,
2H), 7.35-7.39 (m, 2H) Example 252 (s) -1- (3-furyl)
Methylthio) -3-[(s) -2- (4-methoxyphen)
Noxyacetylamino) -4-methylvalerylamino]
Preparation of 2-heptanone (Compound No. 742 of Table-1) IR (neat, cm^-1): 3295, 1715, 16
53 NMR (CDCl₃, Δ): 0.86 (t, J = 7.0)
Hz, 3H), 0.92 to 1.01 (m, 6H), 1.
17-1.38 (m, 5H), 1.45-1.79
(M, 3H), 1.82 (m, 1H), 3.17 (d,
J = 15Hz, 1H), 3.26 (d, J = 15Hz,
1H), 3.54 (s, 2H), 3.77 (s, 3)
H), 4.50 (s, 2H), 4.58 (m, 1H),
4.78 (m, 1H), 6.38 (d, J = 1.2H
z, 1H), 6.65 (d, J = 7.7Hz, 1H),
6.81 to 6.94 (m, 4H), 6.94 (d, J =
8.3 Hz, 1H), 7.36 to 7.39 (m, 2H) Example 253 (s) -3-[(s) -2
-(2,6-Dimethylphenoxyacetylamino) -4
-Methylvalerylamino] -1- (3-furylmethylthio
E) -2-heptanone (Compound No. 745 in Table 1)
Manufacturing Melting point 92 ° C IR (KBr, cm^-1): 3304, 1730, 165
1 NMR (CDCl₃, Δ): 0.87 (t, J = 6.9)
Hz, 3H), 0.97 to 1.04 (m, 6H), 1.
17-1.41 (m, 4H), 1.49-2.01
(M, 5H), 2.26 (s, 6H), 3.19 (d,
J = 15 Hz, 1 H), 3.29 (d, J = 15 Hz,
1H), 3.54 (s, 2H), 4.32 (s, 2
H), 4.60 (m, 1H), 4.80 (m, 1H),
6.38 (m, 1H), 6.69 (d, J = 7.6H
z, 1H), 6.91 to 7.04 (m, 3H), 7.2
8 (d, J = 7.2 Hz, 1H), 7.35 to 7.39
(M, 2H) Example 254 (s) -1- (3-furyl)
Methylthio) -3-[(s) -2- (4-methoxycin
Namoylamino) -4-methylvalerylamino] -2-
Production of heptanone (Compound No. 749 of Table-1) IR (neat, cm^-1): 3269, 1711, 16
49,1602 NMR (CDCl₃, Δ): 0.83 (t, J = 6.6)
Hz, 3H), 0.96 (d, J = 4.3Hz, 6
H), 1.07 to 1.42 (m, 5H), 1.44 to
1.98 (m, 4H), 3.17 (d, J = 15Hz,
1H), 3.26 (d, J = 15Hz, 1H), 3.5
2 (s, 2H), 3.82 (s, 3H), 4.62 ~
4.81 (m, 2H), 6.31 (d, J = 16Hz,
1H), 6.38 (m, 1H), 6.85 (dd, J =
8.8 Hz, 1.7 Hz, 2H), 6.97 (d, J =
8.8 Hz, 1 H), 7.04 (d, J = 8.8 Hz,
1H), 7.32 to 7.39 (m, 2H), 7.42
(Dd, J = 8.8Hz, 1.7Hz, 2H), 7.5
9 (d, J = 16Hz, 1H) Example 255 (s) -1- (3-furyl)
Methylthio) -3-[(s) -4-methyl-2- (4-
Trifluoromethylbenzoylamino) valerylami
No] -2-heptanone (Compound No. 755 in Table 1)
Manufacturing Melting point 140-141 ° C IR (KBr, cm^-1): 3302, 1730, 166
0,1630 NMR (CDCl₃, Δ): 0.83 (t, J = 6.7)
Hz, 3H), 0.99 (d, J = 5.8Hz, 6
H), 1.17 to 1.38 (m, 4H), 1.48 to
1.98 (m, 5H), 3.20 (d, J = 15Hz,
1H), 3.28 (d, J = 15Hz, 1H), 3.5
5 (s, 2H), 4.72 (m, 1H), 4.80
(M, 1H), 6.39 (m, 1H), 6.67 (d,
J = 7.6 Hz, 1H), 6.85 (d, J = 8.1H
z, 1H), 7.35 to 7.41 (m, 2H), 7.6
9 (d, J = 8.3 Hz, 2H), 7.89 (d, J =
8.3Hz, 2H) Example 256 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (2-methyl-3-furylmethylthio)
Preparation of 2-heptanone (Compound No. 756 of Table-1) IR (neat, cm^-1): 3304, 1711, 16
59,1532 NMR (CDCl₃, Δ): 0.87 (t, J = 6.5)
Hz, 3H), 0.95 (d, J = 5.7Hz, 6
H), 1.13 to 1.40 (m, 4H), 1.40
1.73 (m, 4H), 1.87 (m, 1H), 2.2
4 (s, 3H), 3.17 (d, J = 15.4Hz, 1
H), 3.26 (d, J = 14.6 Hz, 1H), 3.
48 (s, 2H), 4.19 (m, 1H), 4.80
(M, 1H), 5.12 (s, 2H), 5.12 (b
r, 1H), 6.30 (br.s, 1H), 6.54
(Br, d, J = 7.8 Hz, 1H), 7.23 (b
r. s, 1H), 7.35 (br.s, 5H) Example 257 (s) -3-((s) -2
-Tert-butoxycarbonylamino-4-methylva
Relylamino) -1- (3-thienylmethoxy) -2-
Production of heptanone (Compound No. 817 of Table-1) Melting point 77-83 ° C IR (KBr, cm^-1): 3335, 1734, 168
0,1661 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.93 (d, J = 5.7Hz, 3
H), 0.94 (d, J = 5.9 Hz, 3H), 1.1
5 to 1.75 (m, 8H), 1.45 (s, 9H),
1.83 (m, 1H), 4.10 (m, 1H), 4.1
4 (d, J = 17 Hz, 1H), 4.21 (d, J = 1
7Hz, 1H), 4.58 (d, J = 12Hz, 1
H), 4.64 (d, J = 12 Hz, 1H), 4.75
Up to 4.93 (m, 2H), 6.65 (d, J = 7.8H)
z, 1H), 7.10 (d, J = 5.0Hz, 1H),
7.27 (m, 1H), 7.32 (dd, J = 5.0H
z, 2.9Hz, 1H) Example 258 (s) -3-((s) -4
-Methyl-2-phenoxyacetylaminovalerylami
No) -1- (3-thienylmethoxy) -2-heptanone
Production of (Compound No. 821 of Table-1) Melting point 76-78 ° C IR (KBr, cm^-1): 3310, 3235, 172
6,1649,1599 NMR (CDCl₃, Δ): 0.85 (t, J = 6.9)
Hz, 3H), 0.92 (d, J = 5.8Hz, 6
H), 1.09 to 1.39 (m, 4H), 1.42
1.98 (m, 5H), 4.13 (d, J = 17Hz,
1H), 4.22 (d, J = 17Hz, 1H), 4.5
2 (s, 2H), 4.55 (m, 1H), 4.58
(D, J = 12 Hz, 1H), 4.64 (d, J = 12
Hz, 1H), 4.79 (m, 1H), 6.56 (d,
J = 7.6Hz, 1H), 6.93 (d, J = 7.9H
z, 2H), 6.94 (m, 1H), 6.99 (dd,
J = 7.4 Hz, 7.4 Hz, 1H), 7.10 (d,
J = 4.9 Hz, 1H), 7.22 to 7.41 (m, 4)
H) Example 259 (s) -3-[(s) -2
-(2,4-dimethoxycinnamoylamino) -4-me
Cylvalerylamino] -1- (3-thienylmethoxy)
Preparation of 2-heptanone (Compound No. 825 of Table-1) Melting point 128-134 ° C IR (KBr, cm^-1): 3300, 1721, 164
0,1599 NMR (CDCl₃, Δ): 0.83 (t, J = 6.9)
Hz, 3H), 0.95 (d, J = 5.9Hz, 6
H), 1.13 to 1.38 (m, 4H), 1.42
1.95 (m, 5H), 3.83 (s, 3H), 3.8
6 (s, 3H), 4.14 (d, J = 17Hz, 1
H), 4.24 (d, J = 17 Hz, 1H), 4.58
(D, J = 12 Hz, 1H), 4.61 (m, 1H),
4.64 (d, J = 12 Hz, 1H), 4.72 (m,
1H), 5.95 (d, J = 8.2Hz, 1H), 6.
40 to 6.55 (m, 3H), 6.74 (d, J = 7.
2Hz, 1H), 7.10 (dd, J = 4.9Hz,
1.2 Hz, 1 H), 7.20 to 7.35 (m, 2
H), 7.38 (d, J = 8.4 Hz, 1H), 7.7
8 (d, J = 16Hz, 1H) Example 260 (s) -3-((s) -2
-Cyclohexyloxycarbonylamino-4-methyl
Valerylamino) -1- (3-thienylmethylthio)-
Preparation of 2-heptanone (Compound No. 761 of Table-1) IR (neat, cm^-1): 3306, 1710, 16
59,1532 NMR (CDCl₃, Δ): 0.88 (t, J = 6.7)
Hz, 3H), 0.95 (d, J = 5.9Hz, 3
H), 0.96 (d, J = 5.8Hz, 3H), 1.1
2 to 1.80 (m, 16H), 1.80 to 1.96
(M, 3H), 3.15 (d, J = 14.7Hz, 1
H), 3.25 (d, J = 14.6 Hz, 1H), 3.
71 (s, 2H), 4.17 (m, 1H), 4.63
(M, 1H), 4.77 (m, 1H), 4.96 (m,
1H), 6.61 (br.d, J = 6.5Hz, 1
H), 7.05 (dd, J = 6.0 Hz, 1.0 Hz,
1H), 7.16 (d, J = 1.8Hz, 1H), 7.
28 (dd, J = 4.9Hz, 2.9Hz, 1H) Example 261 (s) -3-((s) -2
-Cyclohexylmethoxycarbonylamino-4-methyl
Luvalerylamino) -1- (3-thienylmethylthio)
Preparation of 2-heptanone (Compound No. 762 of Table-1) IR (neat, cm^-1): 3308, 1713, 16
59 NMR (CDCl₃, Δ): 0.85 to 1.08 (m,
8H), 0.88 (t, J = 6.4Hz, 3H), 1.
12-1.40 (m, 8H), 1.40-1.98
(M, 10H), 3.15 (d, J = 14.6Hz, 1
H), 3.25 (d, J = 14.2 Hz, 1H), 3.
71 (s, 2H), 3.88 (d, J = 5.9Hz, 2
H), 4.16 (br., 1H), 4.77 (m, 1)
H), 5.02 (br.d, J = 6.5 Hz, 1H),
6.59 (br.d, J = 8.1 Hz, 1H), 7.0
5 (d, J = 4.9 Hz, 1H), 7.16 (s, 1
H), 7.28 (m, 1H) Example 262 (s) -3-((s) -2
-Tert-butoxycarbonylamino-4-methylva
Relylamino) -1- (3-thienylmethylthio) -2
-Production of heptanone (Compound No. 759 of Table-1) Melting point 74.5-75.5 ° C IR (KBr, cm^-1): 3343, 1703, 168
2,1661,1523 NMR (CDCl₃, Δ): 0.87 (t, J = 6.7)
Hz, 3H), 0.94 (d, J = 5.9Hz, 6
H), 1.12 to 1.75 (m, 8H), 1.45
(S, 9H), 1.98 (m, 1H), 3.15 (d,
J = 14.7 Hz, 1H), 3.24 (d, J = 14.4.
7 Hz, 1H), 3.71 (s, 2H), 4.11
(M, 1H), 4.77 (m, 1H), 4.83 (m,
1H), 6.66 (br.d, J = 7.7Hz, 1
H), 7.05 (d, J = 4.9 Hz, 1H), 7.1
6 (d, J = 2.9 Hz, 1H), 7.28 (dd, J
= 4.9Hz, 3.0Hz, 1H) Example 263 (s) -3-((s)-
2-benzyloxycarbonylamino-4-methylvaleri
Luamino) -1- (3-thienylmethylthio) -2-he
Preparation of Ptanone (Compound No. 763 of Table-1) Melting point 65-67 ° C IR (KBr, cm^-1): 3306, 1730, 169
0,1653,1534 NMR (CDCl₃, Δ): 0.87 (t, J = 6.8)
Hz, 3H), 0.95 (d, J = 6.1Hz, 6
H), 1.12 to 1.39 (m, 4H), 1.44 to
1.73 (m, 4H), 1.85 (m, 1H), 3.1
4 (d, J = 14.4Hz, 1H), 3.25 (d, J
= 14.7 Hz, 1H), 3.71 (s, 2H), 4.
20 (m, 1H), 4.77 (ddd, J = 7.8H)
z, 7.8 Hz, 4.4 Hz, 1H), 5.12 (s,
2H), 5.13 (br.s, 1H), 6.54 (b
r. d, J = 7.7 Hz, 1H), 7.05 (d, J =
5.0 Hz, 1H), 7.16 (br.s, 1H),
7.29 (dd, J = 5.0 Hz, 3.1 Hz, 1
H), 7.35 (br.s, 5H) Example 264 (s) -3-[(s) -2
-(2-Fluorobenzyloxycarbonylamino) -4
-Methylvalerylamino] -1- (3-thienylmethyl
Thio) -2-heptanone (Compound No. 764 of Table-1)
Manufacturing of IR (neat, cm^-1): 3306, 1711, 16
57 NMR (CDCl₃, Δ): 0.87 (t, J = 6.8)
Hz, 3H), 0.94 (d, J = 5.9Hz, 6
H), 1.10 to 1.40 (m, 4H), 1.41
1.79 (m, 4H), 1.85 (m, 1H), 3.1
4 (d, J = 14.7 Hz, 1H), 3.25 (d, J
= 14.6 Hz, 1H), 3.70 (s, 2H), 4.
20 (m, 1H), 4.76 (ddd, J = 7.9H)
z, 7.9 Hz, 4.7 Hz, 1H), 5.19 (s,
2H), 5.19 (br., 1H), 6.57 (br.
d, J = 7.6 Hz, 1H), 7.03 to 7.06
(M, 2H), 7.11 (dd, J = 7.5 Hz, 0.
8 Hz, 1H), 7.16 (br.s, 1H), 7.2
7 (dd, J = 5.3 Hz, 2.1 Hz, 1H), 7.
30-7.41 (m, 2H) Example 265 (s) -3-[(s) -2
-(4-Fluorobenzyloxycarbonylamino) -4
-Methylvalerylamino] -1- (3-thienylmethyl
Thio) -2-heptanone (Compound No. 766 of Table-1)
Manufacturing of Melting point 89-90 ° C IR (KBr, cm^-1): 3316, 1690, 165
1,1528 NMR (CDCl₃, Δ): 0.87 (t, J = 6.8)
Hz, 3H), 0.95 (d, J = 6.1Hz, 6
H), 1.10 to 1.20 (m, 4H), 1.44 to
1.75 (m, 4H), 1.85 (m, 1H), 3.1
5 (d, J = 14.6 Hz, 1H), 3.25 (d, J
= 14.5 Hz, 1H), 3.71 (s, 2H), 4.
19 (m, 1H), 4.77 (ddd, J = 7.8H)
z, 7.8 Hz, 4.6 Hz, 1H), 5.07 (s,
2H), 5.14 (br.d, J = 7.5 Hz, 1
H), 6.53 (br.d, J = 7.7 Hz, 1H),
7.00 to 7.07 (m, 3H), 7.15 (d, J =
1.8 Hz, 1H), 7.27 (dd, J = 5.3H
z, 3.1 Hz, 1H), 7.29 to 7.36 (m, 2
H) Example 266 (s) -3-[(s) -4
-Methyl-2- (1-naphthylmethoxycarbonylami)
No) valerylamino] -1- (3-thienylmethylthio)
E) -2-heptanone (Compound No. 770 of Table-1)
Manufacturing Melting point 82-85 ° C IR (KBr, cm^-1): 3304, 1688, 165
5,1532 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.94 (br.s, 6H), 1.10
˜1.38 (m, 4H), 1.42 to 1.73 (m, 4)
H), 1.85 (m, 1H), 3.15 (d, J = 1)
4.9 Hz, 1H), 3.26 (d, J = 14.1H)
z, 1H), 3.71 (s, 2H), 4.22 (m, 1)
H), 4.76 (m, 1H), 5.13 (br.d, J
= 8.5 Hz, 1H), 5.59 (s, 2H), 6.5
8 (br.d, J = 7.6 Hz, 1H), 7.05
(D, J = 4.8 Hz, 1 H), 7.16 (br.s,
1H), 7.28 (dd, J = 5.0Hz, 3.0H
z, 1H), 7.44 (dd, J = 8.0 Hz, 8.0
Hz, 1H), 7.47 to 7.59 (m, 3H), 7.
83 (dd, J = 7.8Hz, 7.8Hz, 2H),
8.03 (d, J = 7.6Hz, 1H) Example 267 (s) -3-[(s) -4
-Methyl-2- (2-pyridylmethoxycarbonylami)
No) valerylamino] -1- (3-thienylmethylthio)
E) -2-heptanone (Compound No. 772 of Table-1)
Manufacturing IR (neat, cm^-1): 3308, 1713, 16
59,1534 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.95 (d, J = 6.1Hz, 3
H), 0.96 (d, J = 6.1 Hz, 3H), 1.1
5 to 1.35 (m, 4H), 1.45 to 1.77 (m,
4H), 1.85 (m, 1H), 3.15 (d, J = 1
4.6Hz, 1H), 3.24 (d, J = 14.6H
z, 1H), 3.70 (s, 2H), 4.21 (dd
d, J = 9.1 Hz, 9.1 Hz, 5.3 Hz, 1
H), 4.77 (ddd, J = 8.0 Hz, 8.0H
z, 4.8 Hz, 1H), 5.24 (d, J = 2.3H
z, 2H), 5.31 (br.d, J = 5.9 Hz, 1
H), 6.59 (br.d, J = 7.3 Hz, 1H),
7.04 (dd, J = 5.0 Hz, 1.2 Hz, 1
H), 7.15 (br.s, 1H), 7.23 (dd,
J = 7.6 Hz, 5.1 Hz, 1H), 7.28 (d
d, J = 5.0 Hz, 3.0 Hz, 1H), 7.34
(D, J = 7.8 Hz, 1H), 7.70 (ddd, J
= 7.8 Hz, 7.8 Hz, 1.8 Hz, 1H), 8.
59 (d, J = 5.6Hz, 1H) Example 268 (s) -3-[(s) -4
-Methyl-2- (N-oxy-2-pyridylmethoxyca
Rubonylamino) valerylamino] -1- (3-thieni
Rumethylthio) -2-heptanone (Compound number in Table-1
773) manufacturing IR (neat, cm^-1): 3285, 1726, 16
61,1537 NMR (CDCl₃, Δ): 0.85 (t, J = 6.8)
Hz, 3H), 0.96 (d, J = 6.0Hz, 3
H), 0.97 (d, J = 6.2 Hz, 3H), 1.1
4 to 1.37 (m, 4H), 1.47 to 1.77 (m,
4H), 1.85 (m, 1H), 3.16 (d, J = 1
4.8 Hz, 1H), 3.25 (d, J = 14.8H
z, 1H), 3.71 (s, 2H), 4.22 (m, 1)
H), 4.78 (ddd, J = 7.8Hz, 7.8H)
z, 4.6 Hz, 1H), 5.39 (d, J = 6.9H)
z, 2H), 5.45 (d, J = 8.0Hz, 1H),
6.57 (d, J = 7.5 Hz, 1H), 7.05 (d
d, J = 4.9 Hz, 1.2 Hz, 1H), 7.16
(Br.s, 1H), 7.22 to 7.37 (m, 3
H), 7.40 (dd, J = 7.4 Hz, 1.9 Hz,
1H), 8.25 (d, J = 5.8Hz, 1H) Example 269 (s) -3-[(s) -4
-Methyl-2- (3-pyridylmethoxycarbonylami)
No) valerylamino] -1- (3-thienylmethylthio)
E) -2-heptanone (Compound No. 774 of Table-1)
Manufacturing IR (neat, cm^-1): 3304, 1713, 16
61,1537 NMR (CDCl₃, Δ): 0.86 (t, J = 6.7)
Hz, 3H), 0.95 (d, J = 5.7Hz, 6
H), 1.13 to 1.40 (m, 4H), 1.40
1.72 (m, 4H), 1.85 (m, 1H), 3.1
5 (d, J = 14.5Hz, 1H), 3.25 (d, J
= 14.8 Hz, 1H), 3.71 (s, 2H), 4.
20 (m, 1H), 4.78 (ddd, J = 7.9H)
z, 7.9 Hz, 4.6 Hz, 1H), 5.24 (d,
J = 2.4 Hz, 2H), 5.28 (br.d, J =
7.9 Hz, 1 H, 6.55 (br.d, J = 7.0)
Hz, 1H), 7.05 (dd, J = 4.9 Hz, 1.
1 Hz, 1 H), 7.16 (d, J = 1.7 Hz, 1
H), 7.29 (dd, J = 4.8 Hz, 1.9 Hz,
1H), 7.30 (dd, J = 7.7Hz, 4.8H
z, 1H), 7.70 (d, J = 7.7Hz, 1H),
8.57 (dd, J = 4.8 Hz, 1.5 Hz, 1
H), 8.61 (s, 1H) Example 270 (s) -3-[(s) -4
-Methyl-2- (3,4-methylenedioxybenzyloxy)
Cycarbonylamino) valerylamino] -1- (3-ti
Enylmethylthio) -2-heptanone (compounds in Table-1
No. 779) manufacturing Melting point 78-80 ° C IR (KBr, cm^-1): 3299, 1703, 168
4,1649,1526 NMR (CDCl₃, Δ): 0.87 (t, J = 6.8)
Hz, 3H), 0.94 (d, J = 6.0 Hz, 6
H), 1.12 to 1.38 (m, 4H), 1.43 to
1.74 (m, 4H), 1.86 (m, 1H), 3.1
4 (d, J = 14.6 Hz, 1H), 3.25 (d, J
= 14.8 Hz, 1H), 3.71 (s, 2H), 4.
18 (m, 1H), 4.76 (ddd, J = 7.8H
z, 7.8 Hz, 2.3 Hz, 1H), 5.01 (s,
2H), 5.11 (br.d, J = 8.0 Hz, 1
H), 5.96 (s, 2H), 6.55 (br.d, J
= 7.7 Hz, 1H), 6.79 (m, 2H), 6.8
5 (s, 1H), 7.05 (dd, J = 5.0 Hz,
1.1 Hz, 1H), 7.16 (br.s, 1H),
7.29 (dd, J = 5.0Hz, 3.0Hz, 1H) Example 271 (s) -3-[(s) -2
-(2,2-Dimethyl-2,3-dihydro-7-benzo
Furanylmethoxycarbonylamino) -4-methylvale
Rylamino] -1- (3-thienylmethylthio) -2-
Production of heptanone (Compound No. 781 of Table-1) IR (neat, cm^-1): 3304, 1719, 16
59,1532 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.94 (d, J = 6.0 Hz, 6
H), 1.16 to 1.36 (m, 4H), 1.47
(S, 6H), 1.47 to 1.72 (m, 4H), 1.
85 (m, 1H), 3.01 (s, 2H), 3.14
(D, J = 14.4 Hz, 1H), 3.25 (d, J =
14.4 Hz, 1H), 3.71 (s, 2H), 4.2
0 (m, 1H), 4.75 (ddd, J = 7.9 Hz,
7.9 Hz, 4.7 Hz, 1H), 5.10 (d, J =
3.1 Hz, 2H), 5.10 (br., 1H), 6.
62 (br.d, J = 7.2 Hz, 1H), 6.79
(Dd, J = 7.4 Hz, 7.4 Hz, 1H), 7.0
5 (dd, J = 4.9 Hz, 1.2 Hz, 1 H), 7.
05 to 7.18 (m, 3H), 7.28 (dd, J =
5.0Hz, 3.0Hz, 1H) Example 272 (s) -3-((s) -2
-Amino-4-methylvalerylamino) -1- (3-ti
(Enylmethylthio) -2-heptanone hydrochloride (Table 1
Production of compound No. 783) Melting point 121-123 ° C IR (KBr, cm^-1): 3385, 1699, 166
9,1522 NMR (CDCl₃, Δ): 0.93 (br.t, J =
6.7 Hz, 3 H), 1.01 (d, J = 5.5 Hz,
3H), 1.03 (d, J = 5.6Hz, 3H), 1.
26-1.44 (m, 4H), 1.44-1.90
(M, 5H), 3.26 (d, J = 15.2Hz, 1
H), 3.36 (d, J = 15.2 Hz, 1H), 3.
75 (s, 2H), 3.91 (m, 1H), 4.73
(M, 1H), 7.07 (dd, J = 5.1 Hz, 1.
3 Hz, 1H), 7.23 (br.s, 1H), 7.3
6 (dd, J = 5.0Hz, 3.0Hz, 1H) Example 273 (s) -3-((s) -4
-Methyl-2-phenoxyacetylaminovalerylami
No) -1- (3-thienylmethylthio) -2-heptano
(Compound No. 786 of Table-1) Melting point 78-79 ° C IR (KBr, cm^-1): 3314, 1705, 164
9,1534 NMR (CDCl₃, Δ): 0.86 (t, J = 6.8)
Hz, 3H), 0.92 (d, J = 6.2Hz, 3
H), 0.94 (d, J = 6.2 Hz, 3H), 1.1
0 to 1.40 (m, 4H), 1.44 to 1.75 (m,
4H), 1.84 (m, 1H), 3.16 (d, J = 1)
4.7 Hz, 1H), 3.25 (d, J = 14.7H)
z, 1H), 3.72 (s, 2H), 4.53 (s, 2)
H), 4.55 (m, 1H), 4.76 (ddd, J =
7.9Hz, 7.9Hz, 4.5Hz, 1H), 6.5
9 (d, J = 8.0 Hz, 1H), 6.94 (d, J =
8.7 Hz, 2H), 6.95 (br., 1H), 7.
00 to 7.07 (m, 2H), 7.17 (d, J = 1.
1 Hz, 1 H), 7.29 (dd, J = 4.9 Hz,
2.7 Hz, 1 H), 7.35 (d, J = 7.5 Hz,
1H) Example 274 (s) -3-[(s) -4
-Methyl-2- (4-trifluoromethylbenzoyla)
Mino) valerylamino] -1- (3-thienylmethylthio)
E) -2-heptanone (Compound No. 792 of Table-1)
Manufacturing Melting point 131-133 ° C IR (KBr, cm^-1): 3293, 1730, 165
7,1638,1539 NMR (CDCl₃, Δ): 0.82 (t, J = 6.8)
Hz, 3H), 0.99 (d, J = 5.8Hz, 6
H), 1.08 to 1.38 (m, 4H), 1.42
1.91 (m, 5H), 3.17 (d, J = 14.7H
z, 1H), 3.26 (d, J = 14.7Hz, 1
H), 3.73 (s, 2H), 4.64 to 4.93.
(M, 2H), 6.66 (br.d, J = 7.7 Hz,
1H), 6.85 (br.d, J = 7.7Hz, 1
H), 7.06 (d, J = 5.0 Hz, 1H), 7.1
8 (br.s, 1H), 7.28 (dd, J = 4.9H)
z, 2.0 Hz, 1H), 7.69 (d, J = 8.2H)
z, 2H), 7.90 (d, J = 8.0Hz, 2H) Example 275 (s) -1-furfurylchi
O-3-[(s) -2- (2-methoxybenzoylami)
No) -4-methylvalerylamino] -4-phenyl-2
-Production of butanone (Compound No. 793 of Table-1) Melting point 102-103 ° C IR (KBr, cm^-1): 3360, 3297, 172
8,1661, 1626, 1601 NMR (CDCl₃, Δ): 0.92 (d, J = 6.4)
Hz, 3H), 0.94 (d, J = 6.6Hz, 3
H), 1.45 to 1.85 (m, 3H), 2.93 (d
d, J = 14 Hz, 7.8 Hz, 1H), 3.13 (d
d, J = 14 Hz, 7.8 Hz, 1H), 3.17
(D, J = 15 Hz, 1H), 3.25 (d, J = 15
Hz, 1H), 3.64 (s, 2H), 3.92 (s,
3H), 4.62 (m, 1H), 4.96 (m, 1)
H), 6.19 (d, J = 3.1 Hz, 1H), 6.2
9 (m, 1H), 6.99 (d, J = 8.4 Hz, 1
H), 7.05 to 7.18 (m, 7H), 7.34
(M, 1H), 7.49 (td, J = 7.4 Hz, 1.
2 Hz, 1 H), 8.01 (d, J = 7.2 Hz, 1
H), 8.16 (dd, J = 7.8 Hz, 1.2 Hz,
1H) Example 276 (s) -1-furfurylchi
O-3-[(s) -4-methyl-2- (4-trifluor
Romethylbenzoylamino) valerylamino] -4-ph
Phenyl-2-butanone (Compound No. 797 in Table 1)
Manufacturing Melting point 169 ° C IR (KBr, cm^-1): 3297, 1723, 164
0 NMR (CDCl₃, Δ): 0.95 (d, J = 5.3)
Hz, 6H), 1.50 to 1.75 (m, 3H), 2.
97 (dd, J = 14 Hz, 7.6 Hz, 1H), 3.
14 (dd, J = 14 Hz, 7.6 Hz, 1 H), 3.
19 (s, 2H), 3.66 (s, 2H), 4.62
(M, 1H), 5.03 (m, 1H), 6.19 (d,
J = 3.2 Hz, 1H), 6.29 (m, 1H), 6.
57 (d, J = 8.5 Hz, 1H), 6.68 (d, J
= 7.8 Hz, 1H), 7.08 to 7.29 (m, 5
H), 7.35 (m, 1H), 7.70 (d, J = 8.
2Hz, 2H), 7.85 (d, J = 8.2Hz, 2
H) Example 277 (s) -3-((s) -2
-Tert-butoxycarbonylamino-4-methylva
Relylamino) -4-phenyl-1- (3-thienylme)
Tyrthio) -2-butanone (Compound No. 79 of Table 1
8) Manufacturing Melting point 95-99 ° C IR (KBr, cm^-1): 3349, 1709, 166
7,1603 NMR (CDCl₃, Δ): 0.90 (d, J = 6.0)
Hz, 3H), 0.91 (d, J = 6.2Hz, 3
H), 1.28 to 1.50 (m, 1H), 1.44
(S, 9H), 1.50 to 1.77 (m, 2H), 2.
95-3.20 (m, 4H), 3.61 (s, 2H),
4.05 (m, 1H), 4.75 (m, 1H), 5.0
1 (m, 1H), 6.66 (d, J = 7.8Hz, 1
H), 7.02 (m, 1H), 7.07 to 7.19.
(M, 3H), 7.22 to 7.38 (m, 4H) Example 278 (s) -3-((s) -2
-Cyclohexylmethoxycarbonylamino-4-methyl
Luvalerylamino) -4-phenyl-1- (3-thieni
Lumethylthio) -2-butanone (Compound No. 8 in Table-1)
00) production Melting point 81-83 ° C IR (KBr, cm^-1): 3308, 1707, 166
8,1667 NMR (CDCl₃, Δ): 0.85 to 1.05 (m,
8H), 1.12 to 1.50 (m, 4H), 1.50
1.82 (m, 8H), 2.91 to 3.18 (m, 4
H), 3.62 (s, 2H), 3.86 (d, J = 6.
2Hz, 2H), 4.08 (m, 1H), 4.89
(M, 1H), 5.01 (m, 1H), 6.62 (d,
J = 7.9 Hz, 1H), 7.01 (dd, J = 5.0)
Hz, 1.3 Hz, 1H), 7.06 to 7.18 (m,
3H), 7.18 to 7.37 (m, 4H) Example 279 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -4-phenyl-1- (3-thienylmethylthio)
E) -2-butanone (Compound No. 801 of Table-1)
Construction Melting point 104-105 ° C IR (KBr, cm^-1): 3324, 3291, 172
5,1690,1651 NMR (CDCl₃, Δ): 0.90 (d, J = 6.1)
Hz, 6H), 1.31-1.70 (m, 3H), 2.
90 to 3.18 (m, 4H), 3.61 (s, 2H),
4.12 (m, 1H), 4.92 to 5.05 (m, 2
H), 5.09 (s, 2H), 6.59 (d, J = 8.
1Hz, 1H), 7.01 (dd, J = 5.0Hz,
1.3 Hz, 1 H), 7.05 to 7.40 (m, 12
H) Example 280 (s) -3-((s) -2
-Amino-4-methylvalerylamino) -4-phenyl
-1- (3-thienylmethylthio) -2-butanone hydrochloric acid
Production of salt (Compound No. 803 of Table-1) IR (KBr, cm^-1): 3383, 1696, 167
2,1605 NMR (CDCl₃, Δ): 0.97 (d, J = 5.9)
Hz, 3H), 0.99 (d, J = 5.6Hz, 3
H), 1.63 to 1.70 (m, 3H), 2.91 (d
d, J = 14 Hz, 9.0 Hz, 1H), 3.17
(D, J = 15 Hz, 1H), 3.18 (dd, J = 1
4Hz, 9.0Hz, 1H), 3.26 (d, J = 15)
Hz, 1H), 3.67 (s, 2H), 3.82 (t,
J = 7.3 Hz, 1H), 4.99 (dd, J = 9.0)
Hz, 5.8 Hz, 1H), 7.03 (dd, J = 5.
0 Hz, 1.3 Hz, 1 H), 7.15 to 7.38
(M, 7H) Example 281 (s) -3-((s) -4
-Methyl-2-phenoxyacetylaminovalerylami
No) -4-phenyl-1- (3-thienylmethylthio)
Preparation of 4-butanone (Compound No. 804 of Table-1) Melting point 89-91 ° C IR (KBr, cm^-1): 3443, 3291, 173
0,1651,1601 NMR (CDCl₃, Δ): 0.87 (d, J = 6.2)
Hz, 1H), 0.89 (d, J = 6.2Hz, 1
H), 1.42 to 1.74 (m, 3H), 2.93 (d
d, J = 14 Hz, 8.4 Hz, 1H), 3.05
(D, J = 15 Hz, 1H), 3.12 (dd, J = 1
4Hz, 8.4Hz, 1H), 3.13 (d, J = 15)
Hz, 1H), 3.64 (s, 2H), 4.39 (d,
J = 15 Hz, 1H), 4.45 (m, 1H), 4.4
8 (d, J = 15 Hz, 1H), 5.01 (td, J =
7.6 Hz, 6.5 Hz, 1H), 6.65 (d, J =
7.6 Hz, 1 H), 6.75 (d, J = 8.3 Hz,
1H), 6.91 (dd, J = 8.8Hz, 1.1H
z, 2H), 7.00 to 7.39 (m, 11H) Example 282 (s) -3-[(s) -2
-(4-Methoxyphenoxyacetylamino) -4-me
Cylvalerylamino] -4-phenyl-1- (3-thiee
Nylmethylthio) -2-butanone (Compound number in Table-1
Production of 808) Melting point 93-96 ° C IR (KBr, cm^-1): 3279, 1709, 167
6,1647 NMR (CDCl₃, Δ): 0.88 (d, J = 6.1)
Hz, 3H), 0.89 (d, J = 6.1Hz, 3
H), 1.42 to 1.78 (m, 3H), 2.93 (d
d, J = 14 Hz, 7.6 Hz, 1H), 3.05
(D, J = 15 Hz, 1H), 3.12 (dd, J = 1
4Hz, 7.6Hz, 1H), 3.13 (d, J = 15)
Hz, 1H), 3.64 (s, 2H), 3.78 (s,
3H), 4.33 (d, J = 15Hz, 1H), 4.4
3 (d, J = 15 Hz, 1H), 4.46 (m, 1
H), 5.0 (td, J = 7.6 Hz, 6.5 Hz, 1
H), 6.64 (d, J = 7.7 Hz, 1H), 6.7
5 (d, J = 8.2 Hz, 1H), 7.01 (s, 4
H), 7.02 (dd, J = 5.0 Hz, 1.3 Hz,
1H), 7.07 to 7.32 (m, 7H) Example 283 (s) -3-[(s) -2
-(2-Methoxybenzoylamino) -4-methylvale
Rylamino] -4-phenyl-1- (3-thienylmethy!
(Luthio) -2-butanone (Compound No. 813 of Table-1)
Manufacturing of Melting point 115-117 ° C IR (KBr, cm^-1): 3374, 3343, 173
4,1665,1628,1601 NMR (CDCl₃, Δ): 0.92 (d, J = 6.5)
Hz, 3H), 0.95 (d, J = 6.6Hz, 3
H), 1.47 to 1.82 (m, 3H), 2.92 (d
d, J = 14 Hz, 7.9 Hz, 1H), 3.04 to
3.20 (m, 3H), 3.63 (s, 2H), 3.9
3 (s, 3H), 4.63 (m, 1H), 4.96
(M, 1H), 6.96 to 7.18 (m, 10H),
7.26 (m, 1H), 7.49 (m, 1H), 8.0
2 (d, J = 7.3 Hz, 1H), 8.17 (dd, J
= 7.8Hz, 1.9Hz, 1H) Example 284 (s) -3-[(s) -2
-(4-Formylbenzoylamino) -4-methylvale
Rylamino] -1-furfurylthio-2-heptanone
Production of (Compound No. 726 of Table-1) Melting point 50 ° C (decomposition) IR (KBr, cm^-1): 3290, 1707, 163
7 NMR (CDCl₃, Δ): 0.80 (t, J = 6.8)
Hz, 3H), 0.98 (d, J = 5.8Hz, 6
H), 1.17 to 1.39 (m, 4H), 1.45
1.62 (m, 1H), 1.63 to 1.98 (m, 4
H), 3.26 (d, J = 15 Hz, 1H), 3.37
(D, J = 15 Hz, 1H), 3.73 (s, 2H),
4.65-4.83 (m, 2H), 6.22 (m, 1)
H), 6.29 (m, 1H), 6.86 (d, J = 7.
3 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1
H), 7.36 (m, 1H), 7.81-8.0 (m,
4H), 10.07 (s, 1H) Example 285 (s) -3-((s) -2
-Benzyloxycarbonylamino-4-methylvaleryl
Amino) -1- (3-thienylmethoxy) -2-hepta
Production of Non (Compound No. 819 of Table-1) IR (KBr, cm^-1): 3295, 1728, 169
0,1651 NMR (CDCl₃, Δ): 0.85 (t, J = 6.9)
Hz, 3H), 0.93 (d, J = 6.0 Hz, 6
H), 1.06 to 1.38 (m, 4H), 1.39 to
1.78 (m, 4H), 1.82 (m, 1H), 4.0
2 to 4.24 (m, 3H), 4.57 (d, J = 10H
z, 1H), 4.61 (d, J = 10Hz, 1H),
4.80 (m, 1H), 5.10 (s, 2H), 5.2
2 (d, J = 7.2 Hz, 1H), 6.60 (d, J =
6.8 Hz, 1H), 7.09 (dd, J = 4.0H
z, 0.9 Hz, 1H), 7.24 (m, 1H), 7.
29 to 7.42 (m, 6H) Example 286 (s) -3-[(s) -2
-((S) -2-cyclohexylmethoxycarbonyla
Mino-4-methylvalerylamino) -4-methylvaleri
Lumino] -1-furfurylthio-2-heptanone (Table
-2 Compound No. 842) IR (neat, cm^-1): 3300, 1700, 16
70,1640 NMR (CDCl₃ , Δ): 0.85 to 1.70 (m,
15H), 1.15 to 2.0 (m, 23H), 3.26.
(D, J = 15 Hz, 1H), 3.32 (d, J = 15
Hz, 1H), 3.71 (s, 2H), 3.87 (d,
J = 6.4 Hz, 2H), 4.12 (m, 1H), 4.
42 (m, 1H), 4.69 (m, 1H), 5.03
(D, J = 5.8 Hz, 1 H), 6.22 (d, J =
3.3 Hz, 1H), 6.28 (dd, J = 3.3H
z, 2.1 Hz, 1H), 6.47 (d, J = 7.5H)
z, 1H), 6.76 (m, 1H), 7.35 (d, J
= 2.1Hz, 1H) Reference Example 3 (s) -1-((s) -2-be
Ndyloxycarbonylamino-4-methylvaleryl)-
Preparation of 2-furfurylthioacetylpyrrolidine IR (neat, cm^-1): 3300, 1710, 16
40 NMR (CDCl₃ , Δ): 0.93 (d, J = 5.9)
Hz, 3H), 0.98 (d, J = 6.5Hz, 3
H), 1.48 (dd, J = 6.9 Hz, 6.9 Hz,
2H), 1.64 to 1.80 (m, 2H), 1.84 to
2.28 (m, 3H), 3.30 (d, J = 15Hz,
1H), 3.42 (d, J = 15Hz, 1H), 3.5
9 (m, 1H), 3.70 (s, 2H), 3.82
(M, 1H), 4.57 (m, 1H), 4.74 (d
d, J = 7.9 Hz, 5.9 Hz, 1H), 5.03 to
5.12 (m, 2H), 5.39 (d, J = 6.8H
z, 1H), 6.23 (m, 1H), 6.29 (m, 1)
H), 7.24 to 7.39 (m, 6H) Test Example 1 Thiol protease inhibitory activity
Measurement of Papain (Sigma, P-3125) and Cathepsin B
The inhibitory activity of (Sigma, C-6286) is shown in the literature (Bi
electrical Journal, Volume 201, 18
(Page 9, 1982).
Cathepsin L was isolated from rat kidney (Journal).
of Biochemistry, 100 volumes, 35 pages
, 1986) and its inhibitory activity.
The sex was measured by the same method as that for cathepsin B described above. m
-Calpain was found in rat brain (Journal
  of Biological Chemistry,
259, page 3210, 1984).
It was further purified and its inhibitory activity was found in the literature (Journal
of Biological Chemistry, 2
59, 12489, 1984).
It measured according to it. The results are shown in Table-3 and Table-4.
From Table-3 and Table-4, the compounds of the present invention are papain,
Thios such as cathepsin B, cathepsin L, and m-calpain
It is known that it has a strong inhibitory effect on
Light [0543] [Table 179] [0544] [Table 180][0545] [Table 181]Test Example 2 Confirmation of reversible inhibition According to the measurement of the inhibitory activity of calpain in Test Example 1,
I went to the sea. 54m of imidazole buffer, 500m
CaCl of M₂ 1 μl of solution, 5 m of synthetic substrate described in literature
M solution 4 μl, 10 μl-150 μM inhibitor solution 1
μl, 40 μl of m-calpain solution was added, and at 10 ° C.
After incubation for 0-20 minutes, 100 mM
The enzyme function is stopped by adding 5 μl of EDTA solution. next
Add 900 μl of imidazole buffer and add 5 mM
40 μl synthetic substrate solution and 500 mM CaCl₂ solution
10 μl was added and the decomposition rate of synthetic substrate was 10 minutes at 30 ℃.
Was measured to determine the residual activity of the enzyme. Examples of the inhibitor include Examples 3,113,190
E compound which is an irreversible inhibitor for comparison
It was also measured for -64. The results are shown in Figs.
You 1 to 3, the irreversible inhibitor E-64 was
Depending on the incubation time, the enzyme activity will be
In contrast to the disappearance, all the compounds of the present invention
It has almost the same residual activity as the control. this
Therefore, it can be said that the compound of the present invention is a reversible inhibitor.
It Test Example 3 Acute toxicity test SD male and female rats were treated with the compound of the present invention at 0.5% CMC-N.
Oral administration of suspension in aqueous solution for 7 days
I made a guess. LD of the compound of Example 94₅₀Value is> 200
It was 0 mg / kg. Test Example 4 Formulation Example (1) Tablet The following ingredients are mixed according to a conventional method and compressed by a conventional device.
did. 30 mg of the compound of Example 94 Crystalline cellulose 60mg Corn starch 100mg Lactose 200mg Magnesium stearate 4 mg (2) Soft capsule The following ingredients are mixed according to the usual method and filled in a soft capsule.
It was 30 mg of the compound of Example 94 Olive oil 300mg Lecithin 20mg (3) Formulation for injection Mix the following ingredients in a standard manner and add 1 ml ampoule.
Prepared. 2.5 mg of the compound of Example 106 Sodium chloride 3.5mg Distilled water for injection 1 ml [0552] INDUSTRIAL APPLICABILITY The ketone derivative of the present invention is used for papain
Tepsin B, cathepsin H, cathepsin L, calpain
Has a strong inhibitory activity against thiol proteases such as
In addition, it also has oral absorbability, tissue transferability, and cell membrane permeability.
Being staggered from muscular dystrophy, muscular atrophy, heart
Consciousness during myocardial infarction, stroke, Alzheimer's disease, and head injury
Disorders, movement disorders, multiple sclerosis, peripheral nerve neuropa
Sea, cataract, inflammation, allergy, fulminant hepatitis, osteoporosis
Disease, hypercalcemia, breast cancer, prostate cancer, prostatic hypertrophy, etc.
As a remedy for cancer, or to suppress cancer growth, prevent metastasis,
It can be used as an inhibitor of platelet aggregation.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a drawing showing that the compound of the present invention (the compound of Example 3) reversibly inhibits calpain. FIG. 2 is a drawing showing that the compound of the present invention (compound of Example 113) reversibly inhibits calpain. FIG. 3 is a drawing showing that the compound of the present invention (the compound of Example 190) reversibly inhibits calpain.

Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI Technical display location A61K 31/27 9283-4C 31/34 ABN 7431-4C 31/38 AAM 7431-4C ABB ABE ABF ABJ ABL ACB ADF ADN ADU 37/64 8314-4C C07C 237/10 7106-4H 275/18 7188-4H 275/20 7188-4H 275/28 7188-4H 275/32 7188-4H 311/10 7419-4H 311/12 7419- 4H 311/14 7419-4H 311/16 7419-4H 311/28 7419-4H 311/29 7419-4H 317/14 7419-4H 317/18 7419-4H 317/32 7419-4H 323/39 7419-4H C07D 307/64 333/34 (72) Inventor Toshiro Sakaki 1000 Kamoshida-cho, Midori-ku, Yokohama-shi, Kanagawa Sanryo Kasei Co., Ltd. (72) Inventor Yasuhiro Morinaka, 1000 Kamoshida-cho, Midori-ku, Yokohama, Kanagawa Ryoshi Kasei Co., Ltd., Research Institute (72) Inventor Chisuko Takahashi 1000, Kamoshida-cho, Midori-ku, Yokohama-shi, Kanagawa San Ryo Kasei Co., Ltd. Tail YoshimiKuni Yokohama-shi, Kanagawa-ku, green Kamoshida-cho address 1000 Mitsubishi Kasei Corporation Overall the laboratory (72) inventor Akihiro Tobe, Chiyoda-ku, Tokyo Marunouchi 2-chome No. 5 No. 2 Mitsubishi Kasei Co., Ltd. in

Claims (1)

Claims 1. The following general formula (I): (R ¹⁰ is a C _{3 to} C ₁₅ cycloalkyl group, a C _{3 to} C ₁₅ cycloalkenyl group, and a C ₆ to optionally substituted group.
C ₁₄ aryl group, optionally substituted C _{10 to} C
₁₄ partially hydrogenated aryl groups, fluorenyl groups,
A heterocyclic residue which may have a substituent, a C _{3 to} C ₁₅ cycloalkyloxy group, an optionally substituted C ₆
To C ₁₄ aryloxy group, optionally substituted C _{6 to} C ₁₄ partially hydrogenated aryloxy group, optionally substituted heterocyclic oxy group, and substituent which may have one or more substituents selected from optionally arylthio group C ₆ -C ₁₄ be also have a aralkyloxy group and substituent of the C ₇ -C ₂₀ optionally having C ₁ ~ C
₂₀ alkyl group; C ₃ -C ₁₅ cycloalkyl group; C ₆ -C ₁₄ aryl group optionally having substituents; part of C ₆ -C ₁₄ optionally having substituents hydrogenated aryl group; represents a heterocyclic residue which may have an alkenyl group or substituent of C ₂ -C ₁₀ which may have a substituent. ), R ² , R ⁴ and R ⁶ each independently represent a hydrogen atom or a C ₁ -C ₅ alkyl group;
³ and R ⁵ are each independently a hydrogen atom, C _{7 to} C _20.
Aralkyloxy group, optionally substituted C ₆
To C ₁₄ aryl group, C _{1 to} C ₁₀ alkoxy group or optionally substituted C _{1 to} C ₂₀ alkyl group. R ² and R ³ , and R ⁴ and R ⁵ may together form a nitrogen-containing heterocycle which may have a substituent. R ⁷ is a C ₃ -C ₁₅ cycloalkyl group, a hydroxyl group, or a C ₁ -C ₅ which may be substituted with a heterocyclic residue.
Alkoxy group, C ₆ -C ₁₄ aryloxy group, C ₇
To C ₂₀ aralkyloxy group, C _{1 to} C ₅ alkylthio group optionally substituted with a heterocyclic residue, C _{6 to} C ₁₄ arylthio group, C _{7 to} C ₂₀ aralkylthio group, carboxyl group, It may have one or more substituents selected from a carbamoyl group, a C _{2 to} C ₆ alkoxycarbonyl group, a heterocyclic residue and an optionally substituted C _{6 to} C ₁₄ aryl group. C ₁ -C ₂₀ alkyl group; hydrogen atom; C ₇ -C ₂₀ aralkyloxy group; optionally substituted C ₆ -C ₁₄ aryl group or C ₁ -C ₁₀ alkoxy group , R ⁸ represents a hydrogen atom, a C ₁ -C ₅ alkyl group or an optionally substituted C ₇ -C ₂₀ aralkyl group, or R ⁷ and R ⁸ together form a substituent. A benzylidene group which may have or C _{3 to} C ₁₅
Represents a cycloalkyl group. [Chemical 2] R ⁹ is an aryl group optionally C ₆ -C ₁₄ which may have a substituent or _{- (CH 2) m -X (} X is a hydrogen atom, a hydroxyl group, an alkylthio group of C ₁ ~C _5, C ₂ ~ alkoxycarbonylamino group having C _6, heterocyclic residue which may have a substituent group, an amino group, monoalkylamino group of C ₁ -C _5, a dialkylamino group of C ₂ ~C _10, C ₂ ~C ₆ acylamino group, halogen atom, C ₁ -C ₅ alkoxy group, optionally substituted C ₆ -C ₁₄ aryl group, or optionally substituted C ₆ -C ₁₄ Represents an aryloxy group, and m represents 0 or an integer of 1 to 15). Provided that R ¹ represents a benzyloxycarbonyl group, R ⁴ , R ⁶ and R ⁸ together represent a hydrogen atom, R ⁵ represents a benzyl group, R ⁷ represents a methyl group,
And when n represents 0, -A-R ⁹ does not represent a methylthio group. (2) when A represents -O-, R ⁹ is a hydrogen atom or - (CH _{2) l} -X (l represents an integer of 1 to 15, X are as defined above.) Represents the. [Chemical 3] Represents a C ₂₀ alkyl group. When representing a), R ⁹ is an aryl group optionally C ₆ -C ₁₄ which may have a substituent or -
(CH ₂₎ m -X (X and m are as defined above.) Represents the. R ⁹ and R ¹¹ may combine to form a nitrogen-containing heterocycle which may have a substituent. Further, n represents 0 or 1. ] The ketone derivative represented by these, or its pharmaceutically acceptable salt. 2. The compound according to claim 1, wherein R ¹¹ represents a C _{1 to} C ₁₅ alkyl group which may have a substituent. 3. R ⁹ has — (CH ₂ ) m—X (where X is a hydroxyl group, a C ₁ -C ₅ alkylthio group, a C ₂ -C ₆ alkoxycarbonylamino group, and a substituent group). Good heterocyclic residue, amino group, C ₁ -C ₅ monoalkylamino group, C ₂ -C ₁₀ dialkylamino group, C ₂ -C ₆
An acylamino group, a halogen atom, a C ₁ -C ₅ alkoxy group, an optionally substituted C ₆ -C ₁₄ aryl group or an optionally substituted C ₆ -C ₁₄ aryl It represents an oxy group, and m represents an integer of 1 to 10. ) Is represented, The compound of Claim 2 characterized by the above-mentioned. 4. A compound represented by the formula: (R ¹⁰ is a C _{3 to} C ₁₅ cycloalkyl group, a C _{3 to} C ₁₅ cycloalkenyl group, and a C ₆ to optionally substituted group.
C ₁₄ aryl group, optionally substituted C _{10 to} C
₁₄ partially hydrogenated aryl group, optionally substituted heterocyclic residue, C _{3 to} C ₁₅ cycloalkyloxy group, optionally substituted C _{6 to} C ₁₄ Aryloxy group, optionally substituted C _{6 to} C ₁₄ partially hydrogenated aryloxy group, optionally substituted heterocyclic oxy group, optionally substituted May be C ₇
To C ₂₀ aralkyloxy groups and optionally substituted C _{6 to} C ₁₄ arylthio groups, optionally substituted C _{1 to} C ₁₅ alkyl groups;
C _{3 to} C ₁₅ cycloalkyl group; C _{6 to} C ₁₄ aryl group which may have a substituent; C _{6 to} C ₁₄ partially hydrogenated aryl which may have a substituent group; represents a heterocyclic residue which may have an alkenyl group or substituent of C ₂ -C ₁₀ which may have a substituent. ),
R ⁴ and R ⁶ are each independently a hydrogen atom or C ₁
To C ₅ alkyl group, R ⁵ is a hydrogen atom, an optionally substituted C _{6 to} C ₁₄ aryl group, C _{1 to} C ₁₀
C ₁ -which may have an alkoxy group or a substituent
Represents a C ₁₅ alkyl group, R ⁷ represents a C ₃ -C ₁₅ cycloalkyl group, a hydroxyl group, a C ₁ -C ₅ alkoxy group which may be substituted with a heterocyclic residue, and a C ₆ -C ₁₄ group. Aryloxy group, C ₇ -C ₂₀ aralkyloxy group, C ₁ -C ₅ alkylthio group optionally substituted with a heterocyclic residue, C ₆ -C ₁₄ arylthio group, C ₇ -C ₂₀ aralkyl Thio group, carboxyl group, carbamoyl group, C ₂
To C ₆ optionally have one or more substituents selected from C ₆ alkoxycarbonyl group and heterocyclic residue substituents C ₁
To C ₁₅ alkyl group; hydrogen atom; C _{6 to} C ₁₄ aryl group which may have a substituent or C _{1 to} C ₁₀ alkoxy group, and R ⁸ represents a hydrogen atom. The compound according to claim 3, wherein [Chemical 6] And n represents 0, The compound of Claim 4 characterized by the above-mentioned. 6. A compound represented by the formula: The compound according to claim 5, wherein R ¹⁰ is the same as defined in claim 4. 7. The compound according to claim 6, wherein R ⁹ represents — (CH ₂ ) m—X (X represents a heterocyclic residue which may have a substituent). 8. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier. 9. A pharmaceutical composition for a disease caused by abnormally elevated thiol protease, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 10. A pharmaceutical composition for a disease caused by skeletal muscle breakdown, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 11. The pharmaceutical composition according to claim 10, wherein the disease caused by skeletal muscle breakdown is dystrophy. 12. The pharmaceutical composition according to claim 10, wherein the disease caused by the breakdown of skeletal muscle is muscular atrophy. 13. A pharmaceutical composition for ischemic disease, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 14. The pharmaceutical composition according to claim 13, wherein the ischemic disease is myocardial infarction. 15. The pharmaceutical composition according to claim 13, wherein the ischemic disease is stroke. 16. A pharmaceutical composition for Alzheimer's disease, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 17. A pharmaceutical composition for consciousness disorder or movement disorder caused by head injury, comprising the compound according to claim 1 and a pharmaceutically acceptable carrier. 18. A pharmaceutical composition for a disease caused by nerve cell demyelination, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 19. The pharmaceutical composition according to claim 18, wherein the disease caused by demyelination of nerve cells is multiple sclerosis. 20. The pharmaceutical composition according to claim 18, wherein the disease caused by demyelination of nerve cells is peripheral neuropathy. 21. A pharmaceutical composition for cataract, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 22. A pharmaceutical composition for inflammation, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 23. A pharmaceutical composition for an allergic disease, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 24. A pharmaceutical composition for a liver disease, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 25. The pharmaceutical composition according to claim 24, wherein the liver disease is fulminant hepatitis. 26. A pharmaceutical composition for osteoporosis, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 27. A pharmaceutical composition for hypercalcemia, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 28. A pharmaceutical composition for a disease caused by aberrant activation of the sex hormone receptor, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier. 29. The pharmaceutical composition according to claim 28, wherein the disease caused by abnormal activation of the sex hormone receptor is breast cancer. 30. The disease caused by abnormal activation of sex hormone receptor is prostate cancer.
8. The pharmaceutical composition according to 8. 31. The pharmaceutical composition according to claim 28, wherein the disease caused by abnormal activation of the sex hormone receptor is benign prostatic hyperplasia. 32. A pharmaceutical composition for suppressing cancer growth or preventing metastasis, comprising the compound according to claim 1 and a pharmaceutically acceptable carrier. 33. A pharmaceutical composition for inhibiting platelet aggregation, which comprises the compound according to claim 1 and a pharmaceutically acceptable carrier.