Highly potent and orally active non-peptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 4'-[(4,4-difluoro-5-methylidene-2,3,4,5-tetrahydro-1H-1-benzoazepin-1-y l)carbonyl]-2-phenylbenzanilide derivatives

A series of compounds structurally related to 4'-[(4,4-difluoro-5-methylidene-2,3,4,5-tetrahydro-1H-1-benzoaz epin-1-yl) carbonyl]-2-phenylbenzanilide were synthesized and evaluated for arginine vasopressin (AVP) antagonistic activity. Compounds with a (Z)-olefin geometry at the 5-position of benzoazepine possessed potent affinity for both the V1A and V2 receptors. Further study has shown that one of these derivatives, (Z)-4'-(?4,4-difluoro-5-[(4-dimethylaminopiperidino)carbonylmet hylene]-2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yI?carbonyl)2- phenylbenzanilide monohydrochloride (29, YM-35471), exhibits exceptionally potent affinity for both of V1A and V2 receptors, even when administered orally. The synthesis and pharmacological properties of this compound are detailed in this paper.     

Preparation of highly potent and selective non-peptide antagonists of the arginine vasopressin V1A receptor by introduction of a 2-ethyl-1H-1-imidazolyl group

To find a new series of arginine vasopressin (AVP) V1A receptor antagonists, the influence of the 2-phenyl group of 2-phenyl-4'-[(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanilide (7) was investigated. Replacement of the 2-phenyl group by a 2-ethyl-1H-imidazol-1-yl group was effective in yielding a V1A-selective compound. Moreover, this imidazolyl group was introduced in the same position in YM-35471 (6), and further studies of these compounds were performed. Consequently, we found that the (Z)-4'-({4,4-difluoro-5-[(N-cyclopropylcarbamoyl)methylene]-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl}carbonyl)-2-(2-ethyl-1H-1-imidazol-1-yl)benzanilide (9f) exhibited highly potent affinity and selectivity, and was the most potent antagonist for the V1A receptor among our compounds. The synthesis and pharmacological evaluation of these compounds are described in this paper.     

Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 4'-[5-(substituted methylidene)-2,3,4,5-tetrahydro-1H-1-ben zoazepine-1-carbonyl]benzanilide and 4'-[5-(substituted methyl)-2,3-dihydro-1H-1-benzoazepine-1- carbonyl]benzanilide derivatives

Arginine vasopressin (AVP) has a dual action, i.e. vasoconstriction and water reabsorption via V1A and V2 receptors, and may play a role in a number of diseases, including congestive heart failure (CHF), hypertension, renal disease, edema, and hyponatremia. We have attempted to develop a new series of AVP antagonists for both V1A and V2 receptors based on the hypothesis that the blockade of both V1A and V2 receptors might be beneficial to CHF patients. In this report, a series of compounds structurally related to 4'-[5-(substituted methylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl ]benzanilide (exo-olefin isomer) and 4'-[5-(substituted methyl)-2,3-dihydro-1H-1-benzoazepine-1-carbonyl]benzanilide (endo-olefin isomer) were synthesized and examined to have AVP antagonist activity for both V1A and V2 receptors. As a result, it was found that the (E)-exo-olefin isomers showed more potent binding affinity compared with endo-olefin isomers. Among these (E)-exo-olefin isomers, (E)-N-methyl-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahyd ro-1H-1 -benzoazepin-5-ylidene}acetamide (14) exhibited the most potent binding affinity and (E)-N-methyl-(1-{4-[2-(4-methylphenyl)benzoylamino]benzoyl}-2,3,4,5- tetrahydro-1H-1-benzoazepin-5-ylidene)acetamide (20) exhibited a high AVP antagonist activity for both V1A and V2 receptors after intravenous administration. Details of the synthesis and pharmacological properties of this series are presented.     

Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 4-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanili de derivatives and 4'-(5,6-dihydro-4H-thiazolo[5,4-d][1]benzoazepine-6-carbonyl)benzanilid e derivatives

Arginine vasopressin (AVP) has a dual action mainly in the periphery, i.e., vasoconstriction and water reabsorption via V1A and V2 receptors; it may play a role in a number of diseases, including congestive heart failure (CHF), hypertension, renal disease, edema, and hyponatremia. We have attempted to develop a new series of orally active AVP antagonists for both V1A and V2 receptors based on the hypothesis that the blockade of both V1A and V2 receptors might be beneficial to CHF patients. In this report, a series of compounds structurally related to 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6- carbonyl)benzanilide and 4'-(5,6-dihydro-4H- thiazolo[5,4-d][1]benzoazepine-6-carbonyl)benzanilide were synthesized and examined for AVP antagonist activity for both V1A and V2 receptors. As a result, it was found that the 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbon yl)-2- phenylbenzanilide derivatives showed potent binding affinity for both V1A and V2 receptors. Especially, 4'-(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phe nylbenzanilide monohydrochloride (18, YM087 = conivaptan hydrochloride) exhibited potent binding affinity and AVP antagonist activity, after intravenous administration, for both V1A and V2 receptors. Furthermore, YM087 exhibited the most potent oral activity for the V2 receptor. Details of the synthesis and pharmacological properties of this series are presented.     

A novel dilithiation approach to 3,4-dihydro-2H-1,3-benzothiazines, 3,4-Dihydro-2H-1,3-benzoxazines,and 2,3,4,5-tetrahydro-1,3-benzothiazepines

3,4-Dihydro-2H-1,3-benzothiazines 4, 3,4-dihydro-2H-1,3-benzoxazines 9, and 2,3,4,5-tetrahydro-1,3-benzothiazepines 6 were synthesized by directed ortho-lithiation of thiophenols and phenols and by side-chain lithiation of substituted thiophenols, respectively, in one-pot by reacting with N,N-bis[(benzotriazol-1-yl)methyl]amines 3 as 1,3-biselectrophile synthons.     

Synthesis of 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones: selective antagonists of muscarinic (M3) receptors

Two approaches to tetrahydro-[1H]-2-benzazepin-4-ones of interest as potentially selective, muscarinic (M(3)) receptor antagonists have been developed. Base promoted addition of 2-(tert-butoxycarbonylamino)methyl-1,3-dithiane with 2-(tert-butyldimethylsiloxymethyl)benzyl chloride gave the corresponding 2,2-dialkylated 1,3-dithiane which was taken through to the dithiane derivative of the parent 2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one by desilylation, oxidation and cyclisation via a reductive amination. After conversion into the N-tert-butyloxycarbonyl, N-toluene p-sulfonyl and N-benzyl derivatives , hydrolysis of the dithiane gave the N-protected tetrahydro-[1H]-2-benzazepin-4-ones . However, preliminary attempts to convert these into 5-cycloalkyl-5-hydroxy derivatives were not successful. In the second approach, ring-closing metathesis was used to prepare 2,3-dihydro-[1H]-2-benzazepines which were hydroxylated and oxidized to give the required 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones. Following preliminary studies, ring-closing metathesis of the dienyl N-(2-nitrophenyl)sulfonamide gave the dihydrobenzazepine which was converted into the 2-butyl-5-cyclobutyl-5-hydroxytetrahydrobenzazepin-4-one by hydroxylation and N-deprotection followed by N-alkylation via reductive amination, and oxidation. This chemistry was then used to prepare the 2-[(N-arylmethyl)aminoalkyl analogues , , and . N-Acylation followed by amide reduction using the borane-tetrahydrofuran complex was also used to achieve N-alkylation of dihydrobenzazepines and this approach was used to prepare the 5-cyclopentyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one and the 5-cyclobutyl-8-fluoro-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one . The structures of 2-tert-butyloxycarbonyl-4,4-propylenedithio-2,3,4,5-tetrahydro-[1H]-2-benzazepine and (4RS,5SR)-2-butyl-5-cyclobutyl-4,5-dihydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepine were confirmed by X-ray diffraction. The racemic 5-cycloalkyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones were screened for muscarinic receptor antagonism. For M(3) receptors from guinea pig ileum, these compounds had log(10)K(B) values of up to 7.2 with selectivities over M(2) receptors from guinea pig left atria of approximately 40.     

Stereoselective synthesis of methyl (Z)-(4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene)acetate using a dianion Horner-Wadsworth-Emmons reagent

Stereoselective synthesis of methyl (Z)-(4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene)acetate (1a) is described. Z-selectivity of the Horner-Wadsworth-Emmons (HWE) reaction was obtained based on an investigation of the reaction conditions for introduction of a methylidene group onto the 5-position of benzazepine.     

Conformationally tailored N-[(2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)carbonyl]proline templates as molecular tools for the design of peptidomimetics. Design and synthesis of fibrinogen receptor antagonists

The proline peptide bond was shown by 2D proton NMR studies to exist exclusively in the trans conformation in benzyl (2S)-1-[[(2S)-2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-11], benzyl (2S)-1-[[(2S)-2-methyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-9], and in the corresponding 6-amino and 7-amino carboxylic acids (S,S)-3 and (S,S)-4. On the other hand, the diastereomers (R,S)-11 and (R,S)-9 containing an (R)[2-methyl-6/7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety, and the diastereoisomers (R,S)-3 and (R,S)-4 incorporating an (R)[6/7-amino-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety were found to exist as equilibria of trans(63-83%) and cis(17-37%) isomers. These conformationally defined templates were applied in the construction of RGD mimetics possessing antagonistic activity at the platelet fibrinogen receptor.     

Azoles and Azines: CXIX. Alkylation of 5,5'-(4-Nitrobenzylidene)bis(2-thiobarbituric) Acid and 5-(4-Nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahydro-2H-pyrano[2,3-d:6,5-d']dipyrimidine-4,6(1H,3H)-dione with Haloacetic Acids and Their Esters

5,5'-(4-Nitrobenzylidene)bis(2-thiobarbituric) acid and 5-(4-nitrophenyl)-2,8-dithioxo-5,7,8,9-tetrahydro-2H-pyrano[2,3-d:6,5-d']dipyrimidine-4,6(1H,3H)-dione, similar to unsubstituted 2-thiobarbituric acid, readily react with haloacetic acids and their esters to form regioselectively the S-alkylation products. The alternative routes fo 5,5'-(4-nitrobenzylidene)bis[(4-hydroxy-6-oxo-1,6-dihydropyrimidine-5,2-diyl)sulfanyl]diacetic acids, based on condensation of 4,6-dihydroxypyrimidin-2-ylthioacetic acid with carbonyl compounds followed by cyclodehydration to [(5-(4-nitrophenyl)-4,6-dioxo-3,5,6,7-tetrahydro-4H-pyrano[2,3-d:6,5-d']dipyrimidine-2,8-diyl)di(sulfanyl)]diacetic acid derivatives, are less efficient. Alkylation of 2-thiobarbituric acid with ethyl bromoacetate in ethanol in the presence of alkali yields 5-(2-oxo-2,5-dihydro-1,3-thiazol-4-yl)-2-thiobarbituric acid.     

Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3h-cycloheptimidazol-4-ones and 2-alkyl-3h-cycloheptimidazol-4-ones

Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2'-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2'-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu(4)NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.     

Determination of (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5- tetrahydro-1H-3-benzazepin-7-ol (NNC 01-0687), a novel dopamine D-1 receptor antagonist, in plasma by solid-phase extraction and high-performance liquid chromatography.

A fast and reliable method has been established for the determination of the dopamine D-1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1 H-3- benzazepin-7-ol (NNC 01-0687) in plasma. A combination of reversed-phase extraction on C18 columns and straight-phase high-performance liquid chromatographic analysis with ultraviolet detection at 287 nm resulted in very clean chromatograms. The limit of quantitation was about 1 ng/ml of plasma. Validation of the method showed good selectivity, linearity, recovery, accuracy and precision. Several modifications of the method were possible with little or no influence on the assay.     

Structural studies of palladium complexes with ligands containing the amide group

Summary Complexes of palladium(II) with 2-(acetylamino)benzoic acid, 2-(benzoylamino)benzoic acid, 2-[2-aminobenzoylamino]benzoic acid, 2-hydroxy benzanilide, 2-mercapto benzanilide, maleanilic acid, 2-(amino carbonyl)benzoic acid, 2-[(phenylamino)carbonyl]benzoic acid, 2-[(1-naphthalenylamino)carbonyl]benzoic acid, 2-[(2-aminophenylamino)carbonyl]benzoic acid, salicylanilide, 2-(aminobenzoyl)benzoic acid and 2-aminobenzamide have been prepared and characterized by chemical analyses, molar conductivity measurements, thermal data and i.r., electronic and n.m.r. spectra.     

(Z)-3,3-二甲基-1-(1H-1,2,4-三唑-1-基)-2-丁酮肟(5-芳基-1,3,4-噁二唑-2-基)甲基醚的合成和抑菌活性

以3,3-二甲基-1-（1H-1,2,4-三唑基）-2-丁酮肟为原料,经醚化、肼解及腙化3步反应得到（E）-N'-（取代苯亚甲基）-2-[（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）丁基-2-亚甲氨氧基]乙酰肼（3a~3u）,化合物3与二乙酸碘苯（IBD）反应,合成了21个（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）-2-丁酮肟-（5-芳基-1,3,4-噁二唑-2-基）甲基醚（4a~4u）,化合物4的化学结构经核磁共振谱、高分辨质谱和元素分析确证.采用单晶X射线衍射仪测定了化合物4c的晶体结构.抑菌活性测试结果表明,在500 mg/L浓度下,化合物4k,4f,4j和4n对纹枯病菌的防效率分别为70.9%,60.2%,60.0%和60.6%;在25 mg/L浓度下,化合物4b,4c,4d和4e对菌核病菌的抑制率为71.8%~76.9%.     

An Asymmetric Synthesis of L-694,458, a Human Leukocyte Elastase Inhibitor, via Novel Enzyme Resolution of beta-Lactam Esters

A convergent synthesis of [S-(R,S)]-2-[4-[(4-methylpiperazin-1-yl)carbonyl]phenoxy]-3,3-diethyl-N-[1-[3,4-(methylenedioxy)phenyl]butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates: (S)-3,3-diethyl-4-[4'-[(N-methylpiperazin-1-yl)carbonylphenoxy]-2-azetidinone (2) and (R)-alpha-propylpiperonyl isocyanate (3). Synthesis of beta-lactam 2 was achieved by a novel enantioselective lipase hydrolysis of ester 5 to produce (S)-3,3-diethyl-4-(4'-carboxyphenoxy)-2-azetidinone (6) (60% yield, three cycles, 93% ee) with isolation, epimerization, and recycling of the undesired (R)-ester 5. Isocyanate 3 was prepared by chiral addition of Zn(n-Pr)(2) to piperonal (98% yield, 99.2% ee), azide displacement and reduction to (R)-alpha-propylpiperonylamine (11) (58% yield, 85% ee), crystallization as the D-pyroglutamic acid salt (92% yield, 98.2% ee), and isocyanate formation (98% yield) with phosgene.     

Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.     

Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes

Novel transformations of the amino and carbonyl/nitrile groups in the Gewald thiophenes were studied for thienopyrimidine synthesis. It was found that 2-amino-thiophene-3-carboxamides and ethyl 2-(acetylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbo- xylate did not yield tetrazole derivatives, neither in the reaction with triethyl orthoformate and sodium azide, nor in the reaction with phosphorus oxychloride and sodium azide, correspondingly. On the contrary, derivatives of thieno[2,3-d]pyrimidin-4(3H)-one and thieno[2,3-d][1,3]oxazin-4-one were isolated. New 2-azidothiophenes [2-azido-4,5,6,7-tetra hydro-1-benzothiophene-3-carbonitrile and 2-azido-4,5,6,7-tetrahydro-1-benzothiophen-3-yl(phenyl)methanone] were synthesized and used in anionic domino reactions with activated acetonitriles to yield thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines and/or 2-(5-amino-1H-1,2,3-triazol-1-yl)thiophenes. Finally, a new ring system of thieno[3,2-e]pyrazolo[1,5-a]pyrimidine was synthesized via a domino reaction of ethyl 2-[(2Z)-2-(1-chloro-2-ethoxy-2-oxoethylidene)hydrazino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate with activated acetonitriles.     

Oligothiophene-containing coumarin dyes for efficient dye-sensitized solar cells

We have developed oligothiophene-containing coumarin dyes fully functionalized for dye-sensitized nanocrystalline TiO(2) solar cells (DSSCs). DSSCs based on the dyes gave good performance in terms of incident photon-to-current conversion efficiency (IPCE) in the range of 400-800 nm. A solar energy-to-electricity conversion efficiency (eta) of 7.4% was obtained with a DSSC based on 2-cyano-3-[5'-(1,1,6,6-tetramethyl-10-oxo-2,3,5,6-tetrahydro-1H,4H,10H-11-oxa-3a-aza-benzo[de]anthracen-9-yl)-[2,2']bithiophenyl-5-yl]acrylic acid (NKX-2677) under simulated AM 1.5G irradiation (100 mW cm(-2)) with a mask: short-circuit current density (J(sc)) = 13.5 mA cm(-2); open-circuit voltage (V(oc)) = 0.71 V; fill factor (FF) = 0.77. Transient absorption spectroscopy measurements indicated that electron injection from NKX-2677 to the conduction band of TiO(2) is very rapid (<100 fs), which is much faster than the emission lifetime of the dye (1.0 ns), giving a highly efficient electron injection yield of near unity.     

Synthesis and pharmacological activity of the metabolites of Pratosartan

Three hydroxylated metabolites of 2-propyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (Pratosartan), which is a selective angiotensin II receptor antagonist, were synthesized in confirmation of their structures and in studies of their pharmacological properties. An MTPA ester of the human main metabolite was identified with the synthesized compound by comparing (1)H-NMR spectra, MS spectra, and HPLC retention time. The structure of the human main metabolite was confirmed to be (S)-(-)-2-(1-hydroxypropyl)-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one ((S)-(-)-1). Also, the rat main metabolites were confirmed to be 8-hydroxylated compound (2) and 5-hydroxylated compound (3). These metabolites showed lower antagonistic activity than that of the parent compound.     

Synthesis and characterization of orally active nonpeptide vasopressin V2 receptor antagonists.

The present study was undertaken to evaluate whether a novel series of 2,6-diaza-5-oxobicyclo[5.4.0]undeca-1(7),8,10-triene derivatives exhibited antagonistic activity for vasopressin V1 and V2 receptors. Most of these compounds were synthesized and showed a high affinity potential for V2 receptor and low to moderate affinity potential for V1 receptor. The most potent and V2-selective compound, N-[4-[2,6-diaza-6-[2-(4-methylpiperazinyl)-2-oxoethyl] -5- oxobicyclo[5.4.0]undeca-1(7),8,10-trien-2-yl]-carbonyl]pheny l][2-(4- methylphenyl)phenyl]-formamide (11b), exhibited IC50's of 2.9 nM for the V2 receptor and 200 nM for the V1 receptor, respectively. When administered orally to rat, 11b showed an approximately 18-fold increased urine volume in comparison with control rat.     

Reaction of acetylenedicarboxylic acids esters with 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-1-carbothioamides and 3,4,5,6-tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazepine-3-thiones

The reactions of dimethyl acetylenecarboxylate with 3,4,5,6-tetrahydro-2H-1,2,4-triazepine-3-thiones and 4,5-dihydro-1H-pyrazole-1-carbothioamides are convenient methods for the synthesis of 7,8-dihydrothiazolo[3,2-b][1,2,4]triazepin-3-ones derivatives and methyl esters of (2Z)-[2-(4,5-dihydro-1H-pyrazol-1-yl)-4-oxo-1,3-thiazol-5(4H)-ylidene]acetic acids, respectively. The reaction of methyl propynoates with 4,5-dihydro-1H-pyrazole-1-carbothioamides or with 5,5,7-trimethyl-2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thione gives 2-(4,5-dihydro-1H-pyrazol-1-yl)-4H-1,3-thiazin-4-ones.