3 Methoxypentane Synthesis Essay

Regular Issue

Vol. 23, No. 3, 1985

24 data found. 1 - 24 listed

Communication | Regular issue | Vol 23, No. 3, 1985, pp. 547 - 548
Published online:

DOI: 10.3987/R-1985-03-0547

High-pressure Synthesis of Cryptands with Aliphatic Bridging Units

Marek Pietraszkiewicz, Piotr Salanski, and Janusz Jurczak*

*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland

Abstract

N,N’-Dimethyl diazacoronands react with α,ω-diiodoalkanes under high pressure (10 kbar) to give the bis-quaternary salts which are transformed into cryptands via demethylation with triphenylphosphine.

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Communication | Regular issue | Vol 23, No. 3, 1985, pp. 549 - 551
Published online:

DOI: 10.3987/R-1985-03-0549

An Aromatic Version of Claisen Rearrangements of Ester Silyl Enolates — A Facile Synthesis of 2,3-Disubstituted Furans

Hideo Nomoto, Eiki Shitara, Keiichiro Fukumoto,* and Tetsuji Kametani

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The [3,3]sigmatropic rearrangement of furfuryl ester silyl enolates (4)~(6) was studied and found to proceed under very mild conditions to give the carboxylic acids (13)~(15) after acid treatment.

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Communication | Regular issue | Vol 23, No. 3, 1985, pp. 553 - 556
Published online:

DOI: 10.3987/R-1985-03-0553

Synthesis of Substituted Tetrahydrofurans and Tetrahydropyrans 1. Oxidative Cyclization of p-Methoxystyrene Derivatives with DDQ

Yuji Oikawa, Kiyoshi Horita, and Osamu Yonemitsu*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

In the course of synthetic studies of polyether antibiotics, we tried to develop a new synthetic method of substituted tetrahydrofuran and tetrahydropyran rings. When p-methoxystyrene derivatives having a hydroxy group at a suitable position was treated with DDQ, an oxidative cyclization of E-olefins, not Z-olefins, occurred yielding substituted tetrahydrofurans and tetrahydropyrans, though in low yields.

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Communication | Regular issue | Vol 23, No. 3, 1985, pp. 557 - 562
Published online:

DOI: 10.3987/R-1985-03-0557

Studies on Indenopyridine Derivatives and Related Compounds. IV. Synthesis and Stereochemistry of Ethyl 9,9-Dimethyl-1,2,3,9a-tetrahydro-9H-indezo[2,1-b]pyridine-3-carboxylate and Its Derivatives

Ryuji Yoneda, Tatsuya Terada, Shinya Harusawa, and Takushi Kurihara*

*Faculty of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The simplified analogs of lysergic acid, namely ; 4-diethylphosphoryl or 3-methyl derivatives (15a, 15b, and 22) of ethyl 1,9,9-trimethyl-1,2,3,9a-tetrahydro-9H-indeno[2,1-b]pyridine-3-carboxylate are synthesized. The structure and stereochemistry of these products as well as some intermediates are also discussed.

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Communication | Regular issue | Vol 23, No. 3, 1985, pp. 563 - 566
Published online:

DOI: 10.3987/R-1985-03-0563

A Novel Stereoselective Synthesis of Morphinan Skeleton

Tetsuji Kametani,* Yukio Suzuki, and Toshio Honda

*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

A basic skeleton of morphinan alkaloids was stereoselectively synthesized by employing a thermolysis of a benzocyclobutene derivative.

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Communication | Regular issue | Vol 23, No. 3, 1985, pp. 567 - 569
Published online:

DOI: 10.3987/R-1985-03-0567

A Modified Synthesis of the (+)-8α-phenylsulfonyl-des-AB-cholestane via an Intramolecular Nucleophilic Attack to Epoxide — A Total Synthesis of Vitamine D3

Hideo Nomoto, Hiroshi Kurobe, Keiichiro Fukumoto,* and Tetsuji Kametani

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

An intramolecular alkylation of the phenylsulfonyl epoxide (6), which was readily obtained from the aldehyde (5), gave a separable mixture of the alcohols (7a) and (8a). The alcohol (8a) was then dehydrated via the corresponding mesylate (8b) to afford the olefin (9) which on hydrogenation furnished (+)-8α-phenylsulfonyl-des-AB-cholestane (1). Further this product was converted into vitamin D3 (4).

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Report | Regular issue | Vol 23, No. 3, 1985, pp. 571 - 583
Published online:

DOI: 10.3987/R-1985-03-0571

The 5-Alkoxymethyl-, 5-Alkylthiomethyl-, and 5-Dialkylaminomethylisoxazoles

Ronald G. Micetich,* Chia C. Shaw, Tse W. Hall, Paul Spevak, Robert A. Fortier, Peter Wolfert, Brian C. Foster, and Buljit K. Bains

*Faculty of Pharmacy , University of Alberta, Edmonton, Alberta T6G, 2N8, Canada

Abstract

A variety of methods were used for the preparation of the 5-alkoxymethyl-, 5-alkylthiomethyl-, and 5-dialkylaminomethylisoxazoles. A novel method for the separation of the isomeric mixture of 3-(5-)methoxymethyl-5-(3-)methylisoxazoles (obtained by reaction of 1-methoxypentane-1,3-dione with hydroxylamine), based on the difference in reactivity with n-butyllithium, is described. Methods for the preparation of 5-alkylthimethylisoxazoles from the 5-methylisoxazoles; and 5-alkoxymethylisoxazoles from the 5-hydroxymethylisoxazoles are also reported.

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Report | Regular issue | Vol 23, No. 3, 1985, pp. 585 - 592
Published online:

DOI: 10.3987/R-1985-03-0585

Lithiation Reactions of 5-Alkoxymethyl-, 5-Alkylthiomethyl-, and 5-Dialkylaminomethylisoxazoles

Ronald G. Micetich,* Chia C. Shaw. Tse W. Hall, Paul Spevak, and Buljit K. Bains

*Faculty of Pharmacy , University of Alberta, Edmonton, Alberta T6G, 2N8, Canada

Abstract

The 5-alkoxymethyl- and 5-alkylthiomethylisoxazoles undergo exclusive lateral lithiation at the C-5 methylene, the products reacting separately with methyl iodide, dimethyl disulfide, and carbon dioxide to give after work up the respective 5α-alkoxyethyl, 5α-alkylthioethyl , the mixed acetal, the thioacetal, the α-alkoxy acid and the α-thioalkoxy acid of the isoxazoles. This reaction can be repeated to give the mixed ortho ester, the thio ortho ester, the mixed α-ketal acid, and the mixed-thioketal acid. This method provides a very convenient route to these classes of compounds. The 5-dialkylaminomethylisoxazole is lithiated at the C-4 position.

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Report | Regular issue | Vol 23, No. 3, 1985, pp. 593 - 602
Published online:

DOI: 10.3987/R-1985-03-0593

On the Synthesis of (±)-Mesembranone by the Dissolving Metal Reduction of 4-Aryl-4-aminoethylcyclohexenones. Isolation of N-Methyl-5-(3’,4’-dimethoxyphenyl)-2-azabiocyclo[3.3.1]nonan-8-one

Ignacio H. Sánchez,* María Larraza, Humbert J. Flores, Eduardo Díaz, and Krzysztof Jankowski

The present invention relates to 2-amino-thiazole derivatives, to a process for their preparation, to pharmaceutical compositions containing them and to their use as therapeutic agents, particularly in the treatment of cancer and cell proliferative disorders.

Several cytotoxic drugs such as, e.g. fluorouracil (5-FU) doxorubicin and camptothecins result to damage DNA or to affect cellular metabolic pathways and thus cause, in many cases, an indirect block of the cell cycle. Therefore, by producing an irreversible damage to both normal and tumor cells, these agents result in a significant toxicity and side-effects. In this respect, compounds capable of being highly specific antitumor agents by selectively leading to tumor cell arrest and apoptosis, with comparable efficacy but reduced toxicity than the currently available drugs, are desirable.

It is well known in the art that progression through the cell cycle is governed by a series of checkpoint controls, otherwise referred to as restriction points, which are regulated by a family of enzymes known as the cyclindependent kinases (cdk). In their turn, the cdks themselves are regulated at many levels such as, for instance, binding to cyclins. A normal progression through the cell cycle is controlled by the coordinated activation and inactivation of different cyclin/cdk complexes. In G1, both cyclin D/cdk4 and cyclin E/cdk2 are thought to mediate the onset of S-phase. Progression through S-phase requires the activity of cyclin A/cdk2 whereas the activation of cyclin A/cdc2 (cdk1) and cyclin B/cdc2 are required for the onset of metaphases.

For a general reference to cyclins and cyclin-dependent kinases see, for instance, Kevin R. Webster et al. in Exp. Opin. Invest. Drugs, 1998, Vol. 7(6), 865–887.

Checkpoint controls are defective in tumor cells due, in part, to disregulation of cdk activity. For example, altered expression of cyclin E and cdk's has been observed in tumor cells, and deletion of the cdk inhibitor p27 KIP gene in mice has been shown to result in a higher incidence of cancer. Increasing evidence supports the idea that the cdks are rate-limiting enzymes in cell cycle progression and, as such, represent molecular targets for therapeutic intervention. In particular, the direct inhibition of cdk/cyclin kinase activity should be helpful in restricting the unregulated proliferation of a tumor cell.

It has now been found that the 2-amino-1,3-thiazoles of the invention are endowed with cdk/cyclin kinase inhibitory activity and are thus useful in therapy as antitumor agents whilst lacking, in terms of both toxicity and side effects, the aforementioned drawbacks known for currently available antitumor drugs. More specifically, the compounds of this invention are useful in the treatment of a variety of cancers including, but not limited to: carcinoma such as bladder, breast, colon, kidney, liver, lung, including small cell lung cancer, esophagus, gall-bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage, including leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell-lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkett's lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including astrocytoma, neuroblastoma, glioma and schwannomas; other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi's sarcoma.

Due to the key role of cdks in the regulation of cellular proliferation, these 2-amino-1,3-thiazole derivatives are also useful in the treatment of a variety of cell proliferative disorders such as, for instance, benign prostate hyperplasia, familial adenomatosis, polyposis, neuro-fibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and post-surgical stenosis and restenosis. The compounds of the invention can be useful in the treatment of Alzheimer's disease, as suggested by the fact that cdk5 is involved in the phosphorylation of tau protein (J. Biochem., 117, 741–749, 1995). The compounds of this invention, as modulators of apoptosis, could be useful in the treatment of cancer, viral infections, prevention of AIDS development in HIV-infected individuals, autoimmune diseases and neurodegenerative disorder. The compounds of this invention could be useful in inhibiting tumor angiogenesis and metastasis.

The compounds of this invention may also act as inhibitors of other protein kinases, e.g. protein kinase C, her2, raf1, MEK1, MAP kinase, EGF receptor, PDGF receptor, IGF receptor, PI3 kinase, wee1 kinase, Src, Abl and thus be effective in the treatment of diseases associated with other protein kinases.

Several 2-amino-1,3-thiazole derivatives are known in the art. Just few examples among them are 2-acetamido-, 2-propionamido- or 2-butyramido-1,3-thiazole derivatives further substituted by halogen atoms in position 5 of the thiazole ring, which are reported as herbicides in JP 73027467 (Sankyo Co. Ltd.) or U.S. Pat. No. 3,374,082 (The Upjohn Co.); 5-nitro-2-benzamido-1,3-thiazole is reported as pesticide in Ann. Rech. Vet., 22(4), 359–63, 1991; 5-phenyl-2-acetamido-1,3-thiazoles further substituted onto phenyl ring are reported as synthetic intermediates (Chemical Abstracts, 1980, 92:128793); and 5-dimethylaminomethyl- or 5-diethylaminomethyl-2-acetamido-1,3-thiazole, both reported as herbicides in JP 71018564 (Japan Gas Chem Co.). Several other 2-amino-1,3-thiazole derivatives have been reported in the art as useful therapeutic agents. In particular, 5-methyl-1,3-thiazoles further substituted in position 2 of the thiazole ring by a benzothiazinylcarbonylamino moiety, or derivatives thereof, have been described as cyclooxygenase inhibitors; see, for instance, C.A. 126(1997):301540. 2-Benzamido-1,3-thiazoles are disclosed in EP-A-261503 (Valeas S.p.A.) as antiallergic agents; 5-Alkyl-2-phenylalkylcarbonylamino-1,3-thiazoles further substituted onto the phenyl ring with an alkenylcarbonyl or alkynylcarbonyl moieties are disclosed in WO 98/04536 (Otsuka Pharmaceutical Co.) as protein kinase C inhibitors. 5-Arylthio-2-acylamino-1,3-thiazole derivatives are disclosed in EP-A-412404 (Fujisawa Pharm. Co.) as antitumor agents. In addition, among the compounds reported in the art as therapeutic agents, DE 2128941 (Melle-Bezons) discloses 2-aminomethylcarbonylamino-5-chloro-1,3-thiazoles as antiinflammatory, sedative and analgesic agents; the compound 2-diethylaminomethylcarbonylamino-5-chloro-1,3-thiazole being specifically exemplified therein.

Accordingly, the present invention provides the use of a compound which is a 2-amino-1,3-thiazole derivative of formula (I)


wherein

    • R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from:
    • i) straight or branched C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl;
    • ii) C3–C6 cycloalkyl;
    • iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • R1 is an optionally further substituted group selected from:
    • i) straight or branched C1–C8 alkyl or C2–C6 alkenyl;
    • ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring;
    • iii) aryl or arylcarbonyl;
    • iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain;
    • vi) an optionally protected amino acid residue;
      or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for treating cell proliferative disorders associated with an altered cell dependent kinase activity.

According to a preferred embodiment of the invention, the said cell proliferative disorder is selected from the group consisting of cancer, Alzheimer's disease, viral infections, auto-immune diseases or neurodegenerative disorders. Preferably, the cancer is selected from the group consisting of carcinoma, squamous cell carcinoma, hematopoietic tumors of myeloid or lymphoid lineage, tumors of mesenchymal origin, tumors of the central and peripheral nervous system, melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi's sarcoma.

According to another preferred embodiment of the invention, the cell proliferative disorder is selected from the group consisting of benign prostate hyperplasia, familial adenomatosis polyposis, neuro-fibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis glomerulonephritis and post-surgical stenosis and restenosis.

In addition, being useful in the treatment of cell proliferative disorders associated with an altered cell dependent kinase activity, hence cell cycle inhibition or cdk/cyclin dependent inhibition, the compounds of formula (I) of the invention also enable tumor angiogenesis and metastasis inhibition.

As above reported, some of the compounds of formula (I) of the invention have been reported in the art as useful therapeutic agents, for instance as antiinflammatory, sedative and analgesic agents.

Therefore, it is a further object of the present invention a compound which is a 2-amino-1,3-thiazole derivative of formula (I)


wherein

    • R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from:
    • i) straight or branched C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl;
    • ii) C3–C6 cycloalkyl;
    • iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • R1 is an optionally further substituted group selected from:
    • i) straight or branched C1–C8 alkyl or C2–C6 alkenyl;
    • ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring;
    • iii) aryl or arylcarbonyl;
    • iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain;
    • vi) an optionally protected amino acid residue;
      or a pharmaceutically acceptable salt thereof; for use as a medicament; provided that each of R and R1, independently, is not a methyl group and that the compound is not 2-diethylaminomethyl-carbonylamino-5-chloro-1,3-thiazole.

Among the compounds of formula (I) above reported, several derivatives result to be novel.

Therefore, the present invention further provides a compound which is a 2-amino-1,3-thiazole derivative of formula (I)


wherein

    • R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from:
    • i) straight or branched C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl;
    • ii) C3–C6 cycloalkyl;
    • iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • R1 is an optionally further substituted group selected from:
    • straight or branched C1–C8 alkyl or C2–C6 alkenyl;
    • ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring;
    • iii) aryl or arylcarbonyl;
    • iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain;
    • v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain;
    • vi) an optionally protected amino acid residue;
      or a pharmaceutically acceptable salt thereof; provided that:
    • a) R and R1, each independently, are not methyl;
    • b) when R is bromine or chlorine then, R1 is not unsubstituted C2–C4 alkyl or an optionally substituted aminomethyl;
    • c) when R is nitro or phenyl, then R1 is not unsubstituted phenyl.

The compounds of formula (I) may have asymmetric carbon atoms and may therefore exist either as racemic admixtures or as individual optical isomers. Accordingly, all the possible isomers and their admixtures and of both the metabolites and the pharmaceutically acceptable bio-precursors (otherwise referred to as pro-drugs) of the compounds of formula (I), as well as the uses thereof, are also within the scope of the present invention.

In the present description, unless otherwise specified, with the term halogen atom we intend a chlorine, bromine, fluorine or iodine atom.

With the term optionally substituted amino group we intend an amino group wherein one or both hydrogen atoms are optionally replaced by other substituents which are the same or different, as set forth below.

With the term straight or branched C1–C8 alkyl we intend a group such as, for instance, methyl, ethyl, n.propyl, isopropyl, n.butyl, isobutyl, sec-butyl, tert-butyl, n.pentyl, n.hexyl, n.heptyl, n.octyl and the like.

With the term straight or branched C2–C6 alkenyl or alkynyl we intend a group such as, for instance, vinyl, allyl, isopropenyl, 1-, 2- or 3-butenyl, isobutylenyl, pentenyl, hexenyl, ethynyl, 1- or 2-propynyl, butynyl, pentynyl, hexynyl and the like.

With the term C3–C6 cycloalkyl we intend a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

With the term aryl, either as such or as arylalkyl, arylalkenyl, arylcarbonyl and the like, we intend a mono-, bi- or poly- either carbocyclic as well as heterocyclyc hydrocarbon with from 1 to 4 ring moieties, either fused or linked to each other by single bonds, wherein at least one of the carbocyclic or heterocyclic rings is aromatic. Examples of aryl groups are phenyl, indanyl, biphenyl, α- or β-naphthyl, fluorenyl, 9,10-dihydroanthracenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, 1,2-methylenedioxyphenyl, thiazolyl, isothiazolyl, pyrrolyl, pyrrolyl-phenyl, furyl, phenyl-furyl, benzotetrahydrofuran, oxazolyl, isoxazolyl, pyrazolyl, chromenyl, thienyl, benzothienyl, isoindolinyl, benzoimidazolyl, tetrazolyl, tetrazolylphenyl, pyrrolidinyl-tetrazolyl, isoindolinyl-phenyl, quinolinyl, isoquinolinyl, 2,6-diphenyl-pyridyl, quinoxalinyl, pyrazinyl, phenyl-quinolyl, benzofurazanyl, 1,2,3-triazole, 1-phenyl-1,2,3-triazole, and the like.

With the term 3 to 6 membered carbocycle, hence encompassing but not limited to C3–C6 cycloalkyl groups, we also intend an unsaturated carbocyclic hydrocarbon such as, for instance, cyclopentylene or cyclohexylene.

With the term 5 to 7 membered heterocycle, hence encompassing aromatic heterocycles also referred to as aryl groups, we further intend a saturated or partially unsaturated 5 to 7 membered carbocyle wherein one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen and sulphur. Examples of 5 to 7 membered heterocycles, optionally benzocondensed or further substituted, are 1,3-dioxolane, pyran, pyrrolidine, pyrroline, imidazolidine, pyrazolidine, pyrazoline, piperidine, piperazine, N-alkyl-piperazine, morpholine, tetrahydrofuran and the like.

With the term amino acid residue we intend the residue of a natural α-amino acid of formula HOOC—R1, wherein R1 is bonded to the thiazole-NH—C(═O)— moiety and is represented by a —CH(Z)NHY group wherein Z is the characterising portion of the amino acid and Y is hydrogen or a suitable amino protecting group such as, for instance, tertbutoxycarbonyl or benzyloxycarbonyl. Examples of α-amino acids are alanine, isoleucine, glycine, lysine, arginine, cystine, histidine, leucine, proline and the like.

According to the above indicated substituent meanings, any of the above R and R1 groups may be optionally substituted in any of the free positions by one or more groups, for instance 1 to 6 groups, selected from: halogen, nitro, oxo groups (═O), carboxy, cyano, alkyl, perfluorinated alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycyl; amino groups and derivatives thereof such as, for instance, alkylamino, alkoxycarbonylalkylamino, dialkylamino, arylamino, diarylamino or arylureido; carbonylamino groups and derivatives thereof such as, for instance, hydrogenocarbonylamino (HCONH—), alkylcarbonylamino, alkenylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino; oxygen-substituted oximes such as, for instance, alkoxycarbonylalkoxyimino or alkoxyimino; hydroxy groups and derivatives thereof such as, for instance, alkoxy, aryloxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy; carbonyl groups and derivatives thereof such as, for instance, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl; sulfurated derivatives such as, for instance, alkylthio, arylthio, alkylsulphonyl, arylsulphonyl, alkylsulphinyl, arylsulphinyl, arylsulphonyloxy, aminosulfonyl, alkylaminosulphonyl or dialkylaminosulphonyl. In their turn, whenever appropriate, each of the above possible substituents on R and R1 may be further substituted by one or more of the aforementioned groups. Examples of compounds of formula (I) wherein R and R1 groups are substituted by one or more of the aforementioned substituents which, in their turn, are optionally further substituted as set forth above, are given below.

Pharmaceutically acceptable salts of the compounds of formula (I) are the acid addition salts with inorganic or organic, e.g. nitric, hydrochloric, hydrobromic, sulphuric, perchloric, phosphoric, acetic, trifluoroacetic, propionic, glycolic, lactic, oxalic, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic, methanesulphonic, isethionic and salicylic acid, as well as the salts with inorganic or organic bases, e.g. alkali or alkaline-earth metals, especially sodium, potassium, calcium or magnesium hydroxides, carbonates or bicarbonates, acyclic or cyclic amines, preferably methylamine, ethylamine, diethylamine, triethylamine or piperidine.

The compounds of formula (I) may have asymmetric carbon atoms and may therefore exist either as racemic admixtures or as individual optical isomers. Accordingly, the use as an antitumor agent of all the possible isomers and their admixtures and of both the metabolites and the pharmaceutically acceptable bioprecursors (otherwise referred to as pro-drugs) of the compounds of formula (I) are also within the scope of the present invention.

Preferred compounds of formula (I), according to the present invention, are 2-amino-1,3-thiazole derivatives wherein R is a halogen atom or an optionally substituted group selected from a straight or branched C1–C4 alkyl, C3–C6 cycloalkyl, aryl or an arylalkyl with from 1 to 4 carbon atoms within the alkyl chain; R1 is an optionally substituted group selected from straight or branched C1–C4 alkyl or alkenyl, aryl or arylalkyl with from 1 to 4 carbon atoms within the alkyl chain or it is an optionally protected amino acid residue.

Still more preferred compounds, within this class, are the derivatives of formula (I) wherein R is a bromine or chlorine atom or is an optionally substituted group selected from straight or branched C1–C4 alkyl, cyclopropyl, aryl or arylalkyl with from 1 to 2 carbon atoms within the alkyl chain; R1 is an optionally substituted group selected from straight or branched C1–C4 alkyl or alkenyl, aryl or arylalkyl with from 1 to 4 carbon atoms within the alkyl chain or it is an optionally protected amino acid residue.

Another class of preferred compounds of the invention are the compounds of formula (I)


wherein

    • R is a halogen atom or is selected from nitro, amino, alkylamino, hydroxyalkylamino, arylamino, C3–C6 cycloalkyl and straight or branched C1–C6 alkyl which is unsubstituted or substituted by hydroxy, alkylthio, alkoxy, amino, alkylamino, alkoxycarbonylamino, alkoxycarbonylalkylamino, alkylcarbonyl, alkylsulfonyl, alkoxycarbonyl, carboxy or aryl which is unsubstituted or substituted by one or more hydroxy, halogen, nitro, alkoxy, aryloxy, alkylthio, arylthio, amino, alkylamino, dialkylamino, N-alkyl-piperazinyl, 4-morpholinyl, arylamino, cyano, alkyl, phenyl, aminosulfonyl, aminocarbonyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or carboxy groups, or R is an aryl group which is unsubstituted or substituted by one or more hydroxy, halogen, nitro, alkoxy, aryloxy, alkylthio, arylthio, amino, alkylamino, dialkylamino, N-alkyl-piperazinyl, 4-morpholinyl, arylamino, cyano, alkyl, phenyl, aminosulphonyl, aminocarbonyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or carboxy groups;
    • R1 is a straight or branched C1–C6 alkyl group or an aryl group, each being unsubstituted or substituted as defined above for R;
      or a pharmaceutically acceptable salt thereof; provided that:
    • a) R and R1, each independently, are not methyl;
    • b) when R is bromine or chlorine then, R1 is not unsubstituted C2–C4 alkyl or an optionally substituted aminomethyl;
    • c) when R is nitro or phenyl, then R1 is not unsubstituted phenyl.

Examples of preferred compounds of the invention, whenever appropriate in the form of pharmaceutically acceptable salts, e.g. hydrobromide or hydrochloride salt, are the following:

  • 1. ethyl 3-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxopropanoate;
  • 2. N-(5-bromo-1,3-thiazol-2-yl)-2-phenyl-acetamide;
  • 3. N-(5-bromo-1,3-thiazol-2-yl)-benzamide;
  • 4. Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)amino]-4-oxobutanoate;
  • 5. N-(5-Bromo-thiazol-2-yl)-3-hydroxy-propionamide;
  • 6. N-(5-Bromo-1,3-thiazol-2-yl)-4-hydroxybutanamide;
  • 7. N-(5-Bromo-thiazol-2-yl)-2-ethoxy-acetamide;
  • 8. 2-N-[2-(3-pyridyl)-acetyl-amino]-5-bromo-thiazole;
  • 9. 2-N-[2-(3-pyridyl)-acetyl-amino]-5-isopropyl-thiazole;
  • 10. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide;
  • 11. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide
  • 12. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;
  • 13. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;
  • 14. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide;
  • 15. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide;
  • 16. N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;
  • 17. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;
  • 18. N-(5-bromo-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;
  • 19. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;
  • 20. N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;
  • 21. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;
  • 22. N-(5-bromo-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;
  • 23. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;
  • 24. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide;
  • 25. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-acetamide;
  • 26. N-(5-bromo-thiazol-2-yl)-4-sulfamoyl-benzamide;
  • 27. N-(5-isopropyl-thiazol-2-yl)-4-sulfamoyl-benzamide;
  • 28. 4-amino-N-(5-bromo-1,3-thiazol-2-yl)butanamide;
  • 29. 3-amino-N-(5-bromo-1,3-thiazol-2-yl) propionamide;
  • 30. N-(5-isopropyl-1,3-thiazol-2-yl)-butanamide;
  • 31. N-(5-bromo-1,3-thiazol-2-yl)-butanamide;
  • 32. N-(5-chloro-1,3-thiazol-2-yl)-butanamide;
  • 33. N-(5-phenyl-1,3-thiazol-2-yl)-butanamide;
  • 34. N-(5-nitro-1,3-thiazol-2-yl)-butanamide;
  • 35. N-(5-methyl-1,3-thiazol-2-yl)-butanamide;
  • 36. N-(5-benzyl-1,3-thiazol-2-yl)-butanamide;
  • 37. N-(5-isobutyl-1,3-thiazol-2-yl)-butanamide;
  • 38. N-(5-cyclopropyl-1,3-thiazol-2-yl)-butanamide;
  • 39. N-{5-[2-(methylsulfonyl)ethyl]-1,3-thiazol-2-yl}-butanamide;
  • 40. N-[5-(2-methylthioethyl)-1,3-thiazol-2-yl]-butanamide;
  • 41. N-{5-[2-(methoxycarbonyl)ethyl]-1,3-thiazol-2-yl}butanamide;
  • 42. N-[5-(3-methoxy-propyl)-1,3-thiazol-2-yl]-butanamide;
  • 43. N-[5-(2-ethoxy-ethyl)-1,3-thiazol-2-yl]-butanamide;
  • 44. N-[5-(indol-3-yl-methyl)-1,3-thiazol-2-yl]-butanamide;
  • 45. N-[5-(3-oxo-butyl)-1,3-thiazol-2 yl]-butanamide;
  • 46. 2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 47. 2-[3-(2-chloroethoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl) acetamide
  • 48. 2-(4-aminophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 49. 4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 50. 2-(2-amino-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 51. N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-morpholinyl)propoxy]phenyl}acetamide
  • 52. N-(5-isopropyl-1,3-thiazol-2′-yl)-2-{3-[2-(4-morpholinyl)ethoxy]phenyl}acetamide
  • 53. N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(1-pirrolidinyl)propoxy]phenyl}acetamide
  • 54. N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-methyl-1-piperazinyl)propoxy]phenyl}acetamide
  • 55. 2-{3-[2-(dimethylamino)ethoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;
  • 56. 2-{3-[3-(dimethylamino)propoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 57. 2-[4-(dimethylamino)phenyl]-N-(5-isobutyl-1,3-thiazol-2-yl)acetamide
  • 58. 2-(1,3-benzodioxol-5-yl)-N-(5-isobutyl-1,3-thiazol-2-yl)acetamide
  • 59. N-(5-benzyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide
  • 60. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(2-methoxyethoxy)-phenyl]acetamide
  • 61. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methyl-1-piperazinyl)benzamide
  • 62. N-(5-isobutyl-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide
  • 63. N-(5-benzyl-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide
  • 64. 2′-[N-[2′-N′-(ethoxycarbonyl-methyl)-amino]-acetyl]amino-5-bromo-thiazole
  • 65. 2-anilino-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 66. (R)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide
  • 67. (S)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide
  • 68. N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 69. 2,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 70. 3,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 71. 3,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 72. 2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 73. 2,3-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 74. 3-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 75. 2-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 76. 4-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 77. 3-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 78. 4-chloro-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 79. 5-bromo-2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 80. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 81. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 82. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 83. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 84. 2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 85. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 86. 2,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 87. 3,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 88. 2,3,4,5,6-pentafluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 89. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-3-nitrobenzamide
  • 90. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-nitrobenzamide
  • 91. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-nitrobenzamide
  • 92. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-nitrobenzamide
  • 93. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-2-nitrobenzamide
  • 94. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-2-nitrobenzamide
  • 95. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-3-nitrobenzamide
  • 96. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-nitrobenzamide
  • 97. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dinitrobenzamide
  • 98. 5-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrophenyl octanoate
  • 99. N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide
  • 100. N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide
  • 101. N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide
  • 102. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)-3-nitrobenzamide
  • 103. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide
  • 104. 6-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide
  • 105. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide
  • 106. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide
  • 107. 5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide
  • 108. 2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-5-nitrobenzamide
  • 109. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide
  • 110. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide
  • 111. N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitro-4-(trifluoromethyl)benzamide
  • 112. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-bis(trifluoromethyl)benzamide
  • 113. N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-bis(trifluoromethyl)benzamide
  • 114. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)benzamide
  • 115. N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide
  • 116. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide
  • 117. 2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide
  • 118. 5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide
  • 119. 2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide
  • 120. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide
  • 121. methyl 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate
  • 122. methyl 2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate
  • 123. 4-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 124. 3-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 125. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbenzamide
  • 126. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide
  • 127. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide
  • 128. N-(5-isopropyl-1,3-thiazol-2-yl)-4-vinylbenzamide
  • 129. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(2-phenylethynyl)benzamide
  • 130. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-methylbenzamide
  • 131. 2-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 132. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenethylbenzamide
  • 133. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylbenzamide
  • 134. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbenzamide
  • 135. 4-(tert-butyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 136. N-(5-isopropyl-1,3-thiazol-2-yl)-4-isopropylbenzamide
  • 137. N-(5-isopropyl-1,3-thiazol-2-yl)-4-pentylbenzamide
  • 138. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide
  • 139. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethylbenzamide
  • 140. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethylbenzamide
  • 141. 4-acetyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 142. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)benzamide
  • 143. 5-(aminosulfonyl)-2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 144. 5-(aminosulfonyl)-4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 145. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide
  • 146. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide
  • 147. 5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide
  • 148. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide
  • 149. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxybenzamide
  • 150. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide
  • 151. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethoxybenzamide
  • 152. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethoxybenzamide
  • 153. N-(5-isopropyl-1,3-thiazol-2-yl)-2,4-dimethoxybenzamide
  • 154. N-(5-isopropyl-1,3-thiazol-2-yl)-2,3-dimethoxybenzamide
  • 155. N-(5-isopropyl-1,3-thiazol-2-yl)-3-phenoxybenzamide
  • 156. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxybenzamide
  • 157. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenoxybenzamide
  • 158. 2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 159. 4-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 160. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4,5-trimethoxybenzamide
  • 161. 3,4-diethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 162. 3,4,5-triethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 163. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-(methoxymethoxy)benzamide
  • 164. 4-butoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 165. N-(5-isopropyl-1,3-thiazol-2′-yl)-4-propoxybenzamide
  • 166. 4-isopropoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 167. N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-benzodioxole-5-carboxamide
  • 168. 4-(benzyloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 169. 4-(2-cyclohexen-1-yloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 170. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethoxy)benzamide
  • 171. 4-(difluoromethoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 172. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfanyl)benzamide
  • 173. 2-[(4-chlorophenyl)sulfinyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 174. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[(4-nitrophenyl)sulfinyl]benzamide
  • 175. N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(4-methylphenyl)sulfonyl]-3-nitrobenzamide
  • 176. N-(5-isopropyl-1,3-thiazol-2-yl)-3-[trifluoromethyl)sulfanyl]benzamide
  • 177. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-4-(methylsulfanyl)benzamide
  • 178. 2-[(2-cyanophenyl)sulfanyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 179. N˜1,N˜1˜-diethyl-3,6-difluoro-N˜2˜-(5-isopropyl-1,3-thiazol-2-yl)phthalamide
  • 180. 4-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 181. 2-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 182. 4-{[(2,5-dimethoxyanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 183. 4-(hydroxymethyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 184. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl acetate
  • 185. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl 4-(acetylamino)-3-iodobenzoate
  • 186. 4-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 187. N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(2-phenylacetyl)amino]benzamide
  • 188. 4-(acetylamino)-3-iodo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 189. 4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 190. 4-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 191. 3-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 192. 2-(methylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 193. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]benzamide
  • 194. 3-{[5-bromo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 195. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(1H-pyrrol-1-yl)benzamide
  • 196. 2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide
  • 197. 2-(4-bromophenyl)-6-(4-iodophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide
  • 198. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]nicotinamide
  • 199. 2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide
  • 200. 5,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide
  • 201. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-6-methylnicotinamide
  • 202. 2,6-dichloro-5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide
  • 203. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxynicotinamide
  • 204. N-(5-isopropyl-1,3-thiazol-2-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide
  • 205. N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-dimethoxynicotinamide
  • 206. N-(5-isopropyl-1,3-thiazol-2-yl)-2-quinoxalinecarboxamide
  • 207. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide
  • 208. N-(5-isopropyl-1,3-thiazol-2-yl)-8-quinolinecarboxamide
  • 209. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-4-quinolinecarboxamide
  • 210. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide
  • 211. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1H-pyrazole-3-carboxamide
  • 212. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-pyrazole-4-carboxamide
  • 213. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxamide
  • 214. 2-[(2,1,3-benzoxadiazol-5-yloxy)methyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide
  • 215. N-(5-isopropyl-1,3-thiazol-2-yl)-9H-fluorene-1-carboxamide
  • 216. N-(5-isopropyl-1,3-thiazol-2-yl)-7-methoxy-1-benzofuran-2-carboxamide
  • 217. N-(5-isopropyl-1,3-thiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3-carboxamide
  • 218. 2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide
  • 219. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide
  • 220. N-(5-isopropyl-1,3-thiazol-2-yl)-2-naphthamide
  • 221. N-(5-isopropyl-1,3-thiazol-2-yl)-9,10-dioxo-9,10-dihydro-2-anthracenecarboxamide
  • 222. N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-4-carboxamide
  • 223. N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-1-carboxamide
  • 224. N-(5-isopropyl-1,3-thiazol-2-yl)-8-oxo-5,6,7,8-tetrahydro-2-naphthalenecarboxamide
  • 225. N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide
  • 226. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide
  • 227. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-4-carboxamide
  • 228. N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-2-phenyl-1H-indole-5-carboxamide
  • 229. 2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-5-carboxamide
  • 230. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-6-carboxamide
  • 231. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methoxy-1H-indole-2-carboxamide
  • 232. 1-allyl-2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide
  • 233. N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-2-carboxamide
  • 234. 1-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-1H-indole-5-carboxamide
  • 235. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-1,2,3-benzotriazole-5-carboxamide
  • 236. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-isoxazolecarboxamide
  • 237. N-(5-isopropyl-1,3-thiazol-2-yl)-3-thiophenecarboxamide
  • 238. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-thiophenecarboxamide
  • 239. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-thiophenecarboxamide
  • 240. 5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-thiophenecarboxamide
  • 241. N-(5-isopropyl-1,3-thiazol-2-yl)-3-[(2,3,3-trichloroacryloyl)amino]-2-thiophenecarboxamide
  • 242. 5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide
  • 243. N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide
  • 244. N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-nitrophenyl)-2-furamide
  • 245. N-(5-isopropyl-1,3-thiazol-2-yl)-5-(2-nitrophenyl)-2-furamide
  • 246. 5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide
  • 247. N-(5-isopropyl-1,3-thiazol-2-yl)-5-[3-(trifluoromethyl)phenyl]-2-furamide
  • 248. 5-(4-chloro-2-nitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide
  • 249. N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-methyl-2-nitrophenyl)-2-furamide
  • 250. 5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide
  • 251. tert-butyl (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylcarbamate
  • 252. (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl acetate
  • 253. (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl acetate
  • 254. (R,S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 255. (R)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 256. (S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 257. 2-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 258. (R,S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 259. (R)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 260. (S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 261. 3,3,3-trifluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-2-phenylpropanamide
  • 262. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-naphthyl)acetamide
  • 263. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-naphthyl)acetamide
  • 264. 2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 265. 2-(1,3-benzodioxol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 266. 2-(2,4-dinitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 267. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-methyl-1H-indol-3-yl)acetamide
  • 268. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-methyl-1H-indol-3-yl)acetamide
  • 269. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-methoxy-1H-indol-3-yl)acetamide
  • 270. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-benzyloxy-1H-indol-3-yl)acetamide
  • 271. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxy-2-methyl-1H-indol-3-yl)acetamide
  • 272. 2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide
  • 273. 2-(5-bromo-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 274. 2-(5-fluoro-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 275. 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 276. 3-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 277. 4-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide
  • 278. N-(5-isopropyl-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide
  • 279. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-thienyl)acetamide
  • 280. N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-(2-thienyl)acetamide
  • 281. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide
  • 282. 2-(5-chloro-1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 283. 2-(1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 284. 2-[2-(formylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide
  • 285. 2-{2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide
  • 286. 2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide
  • 287. ethyl 2-({[2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(1H-pyrazol-3-yl)ethylidene]amino}oxy)acetate
  • 288. 2-(2-furyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide
  • 289. 2-(5-bromo-3-pyridinyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 290. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide
  • 291. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenyl-3-butenamide
  • 292. N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxo-4-(4-methylphenyl)butanamide
  • 293. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-nitrophenyl)butanamide
  • 294. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbutanamide
  • 295. benzyl 4-[(5-isopropyl-1,3-thiazol-2-yl)amino-4-oxobutylcarbamate
  • 296. methyl 5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate
  • 297. 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide
  • 298. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methoxy-1-naphthyl)-4-oxobutanamide
  • 299. 3-(2-chlorophenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 300. 3-(4-methylphenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 301. 3-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 302. 3-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 303. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylpentanamide
  • 304. 3-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 305. 3-(4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 306. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 307. 3-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide
  • 308. 2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 309. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbutanamide
  • 310. N-(5-isopropyl-1,3-thiazol-2-yl)-5-oxo-5-phenylpentanamide
  • 311. 2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl acetate
  • 312. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-oxo-1,3-dihydro-9H-isoindol-2-yl)phenyl]propanamide
  • 313. 1-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide
  • 314. 1-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide
  • 315. 2-(3-bromo-4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 316. 2-(2-nitro-4-trifluoromethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 317. 5-cyclohexyl 1-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}benzyl)(2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate
  • 318. 2-(5,6-dimethyl-1H-benzimidazol-1-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 319. 2′-[5-(4-chlorophenyl)-2H-1,2,3,4-tetraazol-2-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 320. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[5-(1-pyrrolidinyl)-2H-1, 2, 3, 4-tetraazol-2-yl]acetamide
  • 321. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methyl-1-benzothiophen-2-yl)acetamide
  • 322. N-(5-isopropyl-1,3-thiazol-2-yl)-4,4-bis(4-methylphenyl)-3-butenamide
  • 323. 2-cyclopropyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 324. N-{4-bromo-6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexyl}benzamide
  • 325. 2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 326. benzyl 6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexylcarbamate
  • 327. N-1—(5-isopropyl-1,3-thiazol-2-yl)˜N˜4˜-(2-propynyl)-2-butenediamide
  • 328. 4-(2,4-dimethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide
  • 329. 4-(4-benzyloxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide
  • 330. 4-(thiphen-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide
  • 331. benzyl 2-{[(benzyloxy)carbonyl]amino}-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate
  • 332. 4-(1H-indol-3-yl)-N-{3-[(5-isopropyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}butanamide
  • 333. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}phenyl 4-chlorobenzenesulfonate
  • 334. N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[(2-methoxyanilino)carbonyl]amino}benzamide
  • 335. 4-{[2-(isopropylsulfonyl)acetyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 336. N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[2-(phenylsulfanyl)acetyl]amino}benzamide
  • 337. 4-[(diethylamino)sulfonyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 338. 2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 339. 3,5-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 340. 3-{[(2-fluoroanilino)carbonyl]amino]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide
  • 341. N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenyl-5-propyl-1H-pyrazole-4-carboxamide
  • 342. 3-chloro-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide
  • 343. 3-iodo-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide
  • 344. 2-{[(4-chlorophenyl)sulfonyl]methyl}-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide
  • 345. 5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-3-furamide
  • 346. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,3,4,5,6-pentafluorophenyl)acetamide
  • 347. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-fluorophenyl)acetamide
  • 348. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-bromophenyl)acetamide
  • 349. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chlorophenyl)acetamide
  • 350. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenyl)acetamide
  • 351. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-trifluoromethylphenyl)acetamide
  • 352. N-(5-isopropyl-1,3-thiazol-2-yl)-2 (2-methoxyphenyl)acetamide
  • 353. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-dimethoxyphenyl)acetamide
  • 354. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-difluorophenyl)acetamide
  • 355. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4,5-trimethoxyphenyl) acetamide
  • 356. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,6-dichlorophenyl)acetamide
  • 357. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chloro-6-fluorophenyl)acetamide
  • 358. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-dimethoxyphenyl)acetamide
  • 359. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-difluorophenyl)acetamide
  • 360. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-bis-trifluoromethylphenyl)acetamide
  • 361. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylthiophenyl)acetamide
  • 362. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide
  • 363. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-bromophenyl)acetamide
  • 364. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide
  • 365. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-fluorophenyl)acetamide
  • 366. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)acetamide
  • 367. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-trifluoromethylphenyl)acetamide
  • 368. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylphenyl)acetamide
  • 369. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-dimethylaminophenyl)acetamide
  • 370. 2-[1,1′-biphenyl]-4-yl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 371. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-trifluoromethylphenyl)acetamide
  • 372. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-bromophenyl)acetamide
  • 373. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chlorophenyl)acetamide
  • 374. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-nitrophenyl)acetamide
  • 375. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide
  • 376. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dinitrophenyl)acetamide
  • 377. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dichlorophenyl)acetamide
  • 378. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-difluorophenyl)acetamide
  • 379. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-benzyloxy-3-methoxyphenyl)acetamide
  • 380. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dichlorophenyl)acetamide
  • 381. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-difluorophenyl)acetamide
  • 382. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dimethoxyphenyl)acetamide
  • 383. 2-(2,3-dihydro-1H-inden-5-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide
  • 384. N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenylcyclopropanecarboxamide
  • 385. 2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 386. 2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide
  • 387. N-(5-isopropyl-1,3-thiazol-2-yl)-2,2-diphenylacetamide
  • 388. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenoxy)acetamide
  • 389. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)propanamide
  • 390. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)propanamide
  • 391. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-isobutylphenyl)propanamide
  • 392. N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-phenylacetamide
  • 393. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-phenylpentanamide
  • 394. (E, Z)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-2-butenamide
  • 395. N-(5-isopropyl-1,3-thiazol-2-yl)bicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide
  • 396. N-(5-isopropyl-1,3-thiazol-2-yl)-3-oxo-1-indanecarboxamide
  • 397. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)butanamide
  • 398. tert-butyl (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-1-methyl-2-oxoethylcarbamate
  • 399. tert-butyl (1S,2S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylbutylcarbamate
  • 400. tert-butyl 2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate
  • 401. tert-butyl (1S)-5-amino-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}pentylcarbamate
  • 402. tert-butyl 4-[(imino{[(4-methylphenyl)sulfonyl]amino}methyl)amino]-1-{[(5-isopropyl-1,3-thiazol-yl)amino]carbonyl}butylcarbamate
  • 403. tert-butyl 1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(tritylamino)propylcarbamate
  • 404. tert-butyl (1S)-1-(benzyloxymethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate
  • 405. tert-butyl (1S)-1-benzyl-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate
  • 406. tert-butyl (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(benzylthiomethyl)ethylcarbamate
  • 407. benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-[(5-isopropyl-1,3-thiazol-2-yl) amino]-4-oxobutanoate
  • 408. tert-butyl (2S)-2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-1-pyrrolidinecarboxylate
  • 409. tert-butyl (1S)-1-(1H-indol-3-ylmethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl) amino]-2-oxoethylcarbamate
  • 410. tert-butyl (1S)-1-([(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(methylsulfanyl)propylcarbamate
  • 411. tert-butyl (1S)-2-benzyloxy-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}propylcarbamate
  • 412. tert-butyl (1S)-1-(4-benzyloxybenzyl)-2-[(5-isopropyl-1,3-thiazol-2-yl) amino]-2-oxoethylcarbamate
  • 413. tert-butyl (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylpropylcarbamate
  • 414. tert-butyl (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-methylbutylcarbamate
  • 415. benzyl (4S)-4-[(tert-butoxycarbonyl)amino]-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;
    and the pharmaceutically acceptable salts thereof.

The compounds of formula (I) object of the present invention and the salts thereof can be obtained, for instance, by a process comprising reacting a compound of formula (II)


with a compound of formula (III)
R1—COX  (III)
wherein R and R1 are as defined above and X is hydroxy or a suitable leaving group;
and, if desired, converting a 2-amino-1,3-thiazole derivative of formula (I) into another such derivative of formula (I), and/or into a salt thereof.

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