- INDOLE DERIVATIVES AS ALPHA-1 -ANTITRYPSIN MODULATORS FOR TREATING ALPHA-1 -ANTITRYPSIN DEFICIENCY (AATD)
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Indole derivatives as alpha-l-antitrypsin modulators for treating alpha-l-antitrypsin deficiency (AATD).
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Paragraph 00234; 00316; 00793
(2021/10/11)
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- Synthesis method of 2-alkyl-1,3-propylene glycol compound
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The invention discloses a synthesis method of a 2-alkyl-1,3-propylene glycol compound. The method comprises the following steps: step 1, with 2-alkylacrolein 1D as a raw material, subjecting 2-alkylacrolein 1D and an alcohol compound 1E to an addition reaction under the action of a catalyst to obtain a beta-aldehyde ether intermediate 1F, wherein the catalyst is selected from the group consistingof a 3,4-di(formic ether)-phthalimide compound 1A, 5-formic ether-2,3-naphthalimide compound 1B and a 5,8-di(formic ether)-2,3-naphthalimide compound 1C; and step 2, sequentially carrying out catalytic hydrogenation and ether bond protecting group removal on the intermediate 1F to obtain the 2-alkyl-1,3-propylene glycol compound. According to the method, the raw materials are cheap and easy to obtain, the catalyst can be recycled, reaction conditions are mild, yield reaches up to 70% or above, and cost is greatly reduced.
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- SULPHONAMIDES AND COMPOSITIONS THEREOF FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: wherein the variables shown in Formula AA can be as defined anywhere herein. Compounds AA are modulators of NLRP1 and/or NLRP3
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Page/Page column 537
(2019/05/10)
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- CHEMICAL COMPOUNDS AS INHIBITORS OF INTERLEUKIN-1 ACTIVITY
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The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.
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Paragraph 00882; 00883
(2018/08/12)
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- Synthesis of Enantiomerically Enriched 2-Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3-Diols Mediated by Acetobacter aceti
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The stereoselective desymmetrisation of achiral 2-alkyl-1,3-diols is performed by oxidation of one of the two enantiotopic primary alcohol moieties by means of Acetobacter aceti MIM 2000/28 to afford the corresponding chiral 2-hydroxymethyl alkanoic acids (up to 94 % ee). The procedure, carried out in aqueous medium under mild conditions of pH, temperature and pressure, contributes to enlarge the portfolio of enzymatic oxidations available to organic chemists for the development of sustainable manufacturing processes.
- Brenna, Elisabetta,Cannavale, Flavia,Crotti, Michele,De Vitis, Valerio,Gatti, Francesco G.,Migliazza, Gaia,Molinari, Francesco,Parmeggiani, Fabio,Romano, Diego,Santangelo, Sara
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p. 3796 - 3803
(2016/12/24)
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- Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their antiproliferation activities
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A collective synthesis of 4-hydroxy-2-pyridone alkaloids - specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C - has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 μM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.
- Ding, Feiqing,Leow, Min Li,Ma, Jimei,William, Ronny,Liao, Hongze,Liu, Xue-Wei
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supporting information
p. 2548 - 2554
(2014/10/15)
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- Convergent strategy towards the synthesis of restricted analogues of peloruside A
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A rapid convergent strategy to access unsaturated analogues of peloruside A has been demonstrated. This is depicted as an original C11-C12 aldol connection between a C12-C20 ketone fragment and a C2-C11 pyran fragment bearing an aldehyde function, with high yield and a good level of diastereoselectivity. The desired unsaturated macrocycle was obtained by a late-stage ring closing metathesis reaction.
- Zimmermann, Nicolas,Pinard, Pierre,Carboni, Bertrand,Gosselin, Pascal,Gaulon-Nourry, Catherine,Dujardin, Gilles,Collet, Sylvain,Lebreton, Jacques,Mathe-Allainmat, Monique
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p. 2303 - 2315
(2013/05/09)
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- Total synthesis of (-)-18-epi-peloruside A: An alkyne linchpin strategy
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A convergent synthetic route toward cytotoxic agent peloruside A that hinges on the use of an alkyne linchpin to assemble the natural product is described. Other highlights of this synthesis include an asymmetric desymmetrization reaction of a 1,3-diol, a one-pot conversion of a dibromoolefin to a stereodefined enone, and a diastereoselective aldol condensation. Misassignment of the absolute stereochemistry of the C18 stereocenter in our synthesis provided the natural product epimeric at the C18 ethyl stereocenter.
- Trost, Barry M.,Michaelis, David J.,Malhotra, Sushant
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supporting information
p. 5274 - 5277
(2013/11/06)
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- A stereoselective synthesis of the C9-C19 subunit of (+)-peloruside A
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The stereoselective synthesis of a C9-C19 fragment of the potent antitumor agent peloruside A is disclosed. The C11 stereogenic centre was created by a vinylogous Mukaiyama aldol reaction following Carreira's protocol, with excellent stereocontrol. The C13 stereogenic centre was introduced by a substrate controlled reduction. The C15 stereocentre was fashioned using Noyori's asymmetric transfer hydrogenation while the Z-trisubstituted double bond was formed by a regioselective hydrostannation of an alkyne followed by methylation of the resultant vinyl stannane using Lipshutz's protocol. The C18 chiral centre was introduced by a chemoenzymatic route.
- Raghavan, Sadagopan,Vinoth Kumar
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supporting information
p. 2847 - 2858
(2013/05/08)
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- Non-canonical regioisomerizations and a 'Diels-Alderase' are likely essential in the biosynthesis of Spiculoic acid A
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The regiochemistry of dehydration and cyclization steps of the linear biosynthetic precursor of the polyketide natural product Spiculoic acid A (1) were examined. Herein we describe the synthesis of polyene-containing aldehyde 21, a counterpart to the metabolite's putative polyketide intermediate and demonstrate its inability to undergo facile IMDA chemistry. These results suggest the involvement of a non-canonical regioisomerization in the biosynthesis of 1, and that the IMDA reaction is likely enzyme-catalyzed.
- Pinto, Atahualpa,Boddy, Christopher N.
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supporting information; experimental part
p. 5253 - 5256
(2012/09/07)
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- Optically active N- and C-terminal building blocks for the synthesis of peptidyl olefin peptidomimetics
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Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. The N-terminal side of the C=C bond could be easily prepared in an optically pure form from α-amino acids. Synthesis of C-terminal building blocks in an optically pure form is more challenging. We developed a chemoenzymatic stereoselective approach to such optically active C-terminal building blocks to be assembled into peptidyl olefins by a variety of reactions. They include an electrophilic aldehyde and nucleophilic sulfone, phosphonium salt, phosphonate, and diselenide. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection- hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final building blocks.
- Mirilashvili, Sima,Chasid-Rubinstein, Naama,Albeck, Amnon
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experimental part
p. 4671 - 4686
(2010/10/19)
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- Esters of 2,5-multisubstituted-1,3-dioxane-2-carboxylic acid: their conformational analysis and selective hydrolysis
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The carbomethoxy group at the C2 position of the 2,5-multisubstituted 1,3-dioxanes prefers the axial conformation rather than the equatorial one due to an anomeric effect. The trans isomers of the 5-monosubstituted compounds are more selectively hydrolyzed than the cis isomers. Based on the calculated results, hydrolysis to the trans isomers is attributed to the larger carbonyl charges of the trans than those of the cis isomers. The anomeric and homoanomeric effects will explain the axial preference of the carbomethoxy group and selective hydrolysis to the trans isomers. Furthermore, the calculated stability between the cis and trans isomers is in good agreement with the experimental results in the equilibrium state.
- Harabe, Tetsuji,Matsumoto, Takatoshi,Shioiri, Takayuki
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experimental part
p. 4044 - 4052
(2009/10/02)
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- Optically active γ-hydroxy sulfone Julia reagents for the synthesis of peptidyl olefin peptidomimetics
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Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. We developed a chemoenzymatic stereoselective approach to optically active γ-hydroxy sulfones to be assembled into peptidyl olefins by the Julia reaction. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection-hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final sulfone building block. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Mirilashvili, Sima,Chasid-Rubinstein, Naama,Albeck, Amnon
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supporting information; experimental part
p. 3461 - 3464
(2009/04/14)
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- Pheromones and analogs from Neozeleboria wasps and the orchids that seduce them: a versatile synthesis of 2,5-dialkylated 1,3-cyclohexanediones
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Chiloglottone, a wasp pheromone and attractant of sexually deceptive Chiloglottis orchids, and several structural analogs were synthesized. The synthetic approach is facile, high yielding and versatile, enabling rapid divergence to generate dialkylated analogs of chiloglottone. The key transformation was an organocadmium-mediated desymmetrization of glutaric anhydride derivatives. This library of synthetic 2,5-dialkylated 1,3-cyclohexanediones may assist in future identification of natural products in further species.
- Poldy, Jacqueline,Peakall, Rod,Barrow, Russell A.
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p. 2446 - 2449
(2008/09/20)
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- Conformational analysis and selective hydrolysis of 2,5-disubstituted-1,3-dioxane-2-carboxylic acid esters
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5-Alkyl-2-methyl-2-carbomethoxy-1,3-dioxanes were found to have a cis preferential configuration in the equilibrium state, and the ester hydrolysis rate of the trans-isomers was faster than that of the cis-isomers. Conformational analysis and charge calculation of the carbomethoxy group in both dioxanes elucidated this selectivity.
- Harabe, Tetsuji,Matsumoto, Takatoshi,Shioiri, Takayuki
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p. 1443 - 1446
(2008/02/02)
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- 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
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The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.
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Page/Page column 21
(2010/10/20)
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- Ring-opening of 2,3-epoxy-1-propanol with R3Al: Unprecedented regiochemical switching simply achieved by changing alkyl substituents of aluminium reagent
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Several control experiments were designed to optimize the reaction of 2,3-epoxy-1-propanol with R3Al (R = Me, Et or iBu) and to probe for the nature of aluminium-bound alkyl groups that influence the reactivity and selectivity. The reported studies revealed that the Et 3Al mediated reaction leads to the C-2 product in contrast to the well-known C-3 substitution promoted by Me3Al.
- Lewiński, Janusz,Horeglad, Pawe?,Tratkiewicz, Ewa,Justyniak, Iwona,Ochal, Zbigniew
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p. 3697 - 3699
(2007/10/03)
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- 4-((PHENOXYALKYL)THIO)-PHENOXYACETIC ACIDS AND ANALOGS
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The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.
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Page/Page column 54
(2010/02/11)
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- Total synthesis of pyridovericin: studies toward the biomimetic synthesis of pyridomacrolidin.
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[reaction: see text] The total synthesis of the novel metabolite pyridovericin 1 is reported. The synthesis of this key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily available 2,4-dihydroxypyridine.
- Baldwin, Jack E,Adlington, Robert M,Conte, Aurelia,Irlapati, Nageswara Rao,Marquez, Rodolfo,Pritchard, Gareth J
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p. 2125 - 2127
(2007/10/03)
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- Total synthesis of rutamycin B and oligomycin C
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The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)-oligomycin C (2) is described. The approach relied on the synthesis and coupling of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate fragment 4. The preparation of the spiroketal fragments was achieved using chiral (E)-crotylsilane bond construction methodology, which allowed the introduction of the stereogenic centers prior to spiroketalization. The present work details the synthesis of the C19-C28 and C29-C34 subunits as well as their convergent assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6 and 8 to afford the individual linear spiroketal intermediates 5a and 5b, respectively. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketal-coupling partners 40 and 41. The requisite polypropionate fragment was assembled in a convergent manner using asymmetric crotylation methodology for the introduction of six of the nine-stereogenic centers. The use of three consecutive crotylation reactions was used for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of 35 with the chiral α-methyl aldehyde 39 was used for the introduction of the C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17 advanced intermediate 36. A two-carbon homologation completed the construction of the polypropionate fragment 38. The completion of the synthesis of the two macrolide antibiotics was accomplished by the union of two principal fragments that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling reaction between the terminal vinylstannanes of the individual spiroketals 3a and 3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47 were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi reaction conditions. Deprotection of these macrolides completed the synthesis of the rutamycin B and oligomycin C.
- Panek,Jain
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p. 2747 - 2756
(2007/10/03)
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- Reduction of Diethyl Alkylidenemalonates and Ethyl Propylideneacetoacetate with Complex Metal Hydrides
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Reduction of diethyl alkylidenemalonates and ethyl propylideneacetoacetate with complex metal hydrides occurs at the olefinic moiety. The reduction with NaBH4 in t-BuOH-MeOH yields saturated 1,3-diols; LiAlH4 as reducing agent gives rise to corresponding saturated esters. With NaAlH4 in THF, a mixture of products is formed, which contains considerable amounts of the initial ester and low-boiling compounds; ethyl propylideneacetoacetate is also reduced to ethyl propylacetoacetate. The system NaBH4-AlBr3 in THF almost does not reduce diethyl isopropylidenemalonate, whereas under the same conditions ethyl propylideneacetoacetate is converted into ethyl 2-(1-hydroxyethyl)pentanoate.
- Kuznetsov,Alekseeva,Gren'
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p. 396 - 399
(2007/10/03)
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- Total asymmetric syntheses of (1S,2S)-norcoronamic acid, and of (1R,2R)- and (1S,2S)-coronamic acids from the diastereoselective cyclization of 2-(N-benzylideneamino)-4-chlorobutyronitriles
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(3R)-2-(N-Benzylideneamino)-4-chloro-3-methylbutyronitrile 3, prepared from the commercially available methyl (2S)-3-hydroxy-2-methyl propionate 5 (96percent ee), readily underwent potassium carbonate induced cyclization to provide, after acid hydrolysis (6 N HCl) and chromatography, the (1S,2S)-norcoronamic acid 1a with 88percent diastereoselectivity and above 95percent enantiomeric excess.From (2R)-2-(hydroxymethyl)butyl acetate 23 (above 88percent ee) obtained by enzymatic enantioselective hydrolysis with lipase PS, was prepared the (3S)-2-(N-benzylideneamino)-3-(chloromethyl)valeronitrile 29, which after base-induced cyclization (K2CO3) and acid (6 N HCl) or basic (0.8 N NaOH) hydrolysis led to the non-natural (1R,2R)-coronamic acid 18 (>88percent ee).Also from this same acetate (2R)-23 was prepared the (3R)-3-(chloromethyl)-2-pentanenitrile 37, which provided the (1S,2S)-coronamic acid 17 (above 88percent ee) after base-induced cyclization (K2CO3 or LDA) and acid hydrolysis (6 N HCl).It is noteworthy that these short synthetic sequences, which do not require any expensive chiral auxiliary or optically active precursors, do not alter the enantiomeric purity of the stereogenic centers of these 2,3-methanoamino acids.However, the E diastereoselctivity of these cyclizations was not improved by using bulky N-(diphenylmethylene)amino substituent, contrary to results of some molecular mechanic calculations (MAD).
- Gaucher, Anne,Ollivier, Jean,Marguerite, Jacqueline,Paugam, Renee,Salauen, Jacques
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p. 1312 - 1327
(2007/10/02)
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- Methods and compositions for controlling intraocular pressure with transition metal complexes
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Compositions and methods for controlling intraocular pressure using transition metal complexes are disclosed. Topical ophthalmic and systemic administration of the transition metal complexes is disclosed.
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- Synthesis and Liquid Crystal Properties of Dimethylene Linked Compounds Incorporating the Cyclobutane or Spiroheptane Rings
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The preparation of sixteen dimethylene linked compounds is described heptane ring>, and a comparison is made between the transition temperatures of these compounds and those of the corresponding esters.This comparison once again highlights the fact that the cyclobutane ring should be regarded, in terms of its ability to promote nematic thermal stability, as a "chain stiffener rather than as a ring system.A comparison is also made of the nematic thermal stabilities of the trans-cyclobutane and the spiroheptane systems and of the trans-cyclohexane and the spiroundecane systems.
- Chan, L. K. M.,Gemmell, P. A.,Gray, G. W.,Lacey, D.,Toyne, K. J.
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p. 229 - 246
(2007/10/02)
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- Synthesis and liquid crystal properties of compounds incorporating cyclobutane, spiroheptane and dispirodecane rings
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A number of esters of structure (I) incorporating the cyclobutane, spiroheptane, or dispirodecane rings has been prepared using a diethyl malonate synthesis.Strict comparison of the liquid crystal behaviour amongst the three classes containing a terminal cyano-substituent was not possible because both the cyclobutanes and dispirodecanes are mixtures of cis- and trans-isomers; the spiroheptanes are racemic systems.Using preparative hplc, it was however possible to isolate the pure cis- and trans-isomers of two of the cyano-substituted cyclobutane esters (I; R = alkyl, -X- = --, Y = CN).From the physical data and the results for the corresponding spiroheptane esters, conclusions regarding the effects of these ring systems on liquid crystal behaviour were obtained.The pure cis- and trans-isomers of the cyclobutane ester (I, R = C3H7, -X- = --, Y = CN) have been assessed for the trends in both order parameter and viscosity with temperature; the results support the idea that idea that the trans-cyclobutane ring adopts a more planar conformation at higher temperatures.Keywords: cyclobutane- and related spiro-systems, cis-/trans-isomerism, order parameter, briefringence, viscosity, structure/property relations.
- Chain, L. K. M.,Gemmel, P. A.,Gray, G. W.,Lacey, D.,Toyne, K. J.
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p. 113 - 140
(2007/10/02)
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- STUDY OF THE ANOMERIC EFFECT IN 2-SUBSTITUTED 1,3-DITHIANES
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The conformational analysis of several 2-substituted 1,3-dithianes made possible the evaluation of S-C-Y anomeric interactions, where Y=SCH3,SC6H5,CO2CH3,COC6H5,CO2H and N(CH3)2.The relative magnitude of the effects observed for these groups odithiane(Y)-ΔGocyclohexane(Y)> can be explained in terms of the combined influence of dipole/dipole and two-electron stabilizing interactions (stereoelectronic effect).
- Juaristi, Eusebio,Tapia, Josefina,Mendez, Rodolfo
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p. 1253 - 1264
(2007/10/02)
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- Tobacco smoke chemistry. 1. A chemical and mass spectrometric study of tobacco smoke alkyl 2-hydroxy-2-cyclopentenones.
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A series of alkyl 2-hydroxy-2-cyclopentenones, which comprise biologically and organoleptically active compounds, have been synthesized and subjected to high resolution mass spectrometric studies to clarify structurally significant fragmentation pathways. On the basis of these results, 26 alkyl 2-hydroxy-2-cyclopentenones were identified in the weakly acidic fraction of smoke condensate from American blend type cigarettes, eighteen of which had not been detected in tobacco smoke previously. The utility for identification purposes of the corresponding quinoxaline derivatives, obtained through condensation with o-phenylenediamine, is discussed.
- Arnarp,Enzell,Petersson,Pettersson
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p. 839 - 854
(2007/10/02)
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- LIQUID CRYSTAL MATERIALS WITH SULFUR ATOMS INCORPORATED IN THE PRINCIPAL STRUCTURE: 1. NEW LIQUID CRYSTAL COMPOUNDS WITH 1,3-DITHIANE RING.
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2-(p-Substituted phenyl)-5-alkyl-1,3-dithianes, new liquid crystals, were synthesized by the thioacetalization of the corresponding aldehydes and dithiols. These compounds have characteristic supercooling states, exhibit monotropic liquid crystal phases even in the case of long terminal alkyl substituents. The mesomorphic characteristics of these compounds were different from those of the corresponding 1,3-dioxanes, this must originate in the difference in the molecular width caused by the difference in the atomic volume between sulfur and oxygen.
- Haramoto,Nobe,Kamogawa
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p. 1966 - 1969
(2007/10/02)
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- Enantiotopically Selective Oxidation of α,ω-Diols with the Enzyme Systems of Microorganisms
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Gluconobacter were found to be capable of oxidizing prochiral diols such as 2-substituted propane-1,3-diols 1 and 3-substituted pentane-1,5-diols 4 with distinction of pro-R and pro-S sites of the molecules, in that (-)-(R)-α-substituted β-hydroxypropionic acids 2 and (+)-(3S)-3-substituted δ-valerolactones 5 were obtained, respectively.Oxidation of 3-methylpentane-1,3,5-triol 11 afforded unnatural (+)-(S)-mevalonolactone 12.The steric bulkiness of the substituents on the prochiral center and the distance from the hydroxy group greatly affected the rate and the enantioselectivity of the reaction.
- Ohta, Hiromichi,Tetsukawa, Hatsuki,Noto, Naoko
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p. 2400 - 2404
(2007/10/02)
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- Cyclobutyl substituted derivatives of prostaglandin analogs
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Novel C15 cyclobutyl analogs or derivatives of prostaglandins of the E-, A- and F-classes are useful modifiers of smooth muscle activity. The compounds have valuable pharmacological properties such as platelet antiaggregating agents, gastric antisecretory agents and brochodilating agents.
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- Preparation of 15-deoxy-16-hydroxyprostaglandins
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Analogues of PGE1 having the structural formula, STR1 in which J is R-hydroxymethylene or S-hydroxymethylene; R1 is hydrogen; R2 is hydrogen or together with R4 is a methylene chain of 2 to 3 carbon atoms such that a cycloalkyl of 5 to 6 carbon atoms inclusive is formed; R3 is hydrogen or methyl, or together with R4 is a methylene or a lower alkylated methylene chain of 2 to 5 carbon atoms such that a cycloalkyl or a lower alkylated cycloalkyl of 4 to 7 carbon atoms inclusive is formed, or together with R4 is bicycloalkyl or bicycloalkenyl moiety having the formula: STR2 SUCH THAT A BICYCLOALKYL OR BICYCLOALKENYL COMPOUND IS FORMED, WHEREIN M AND N ARE INTEGERS HAVING A VALUE FROM 0 TO 3, P IS AN INTEGER HAVING A VALUE FROM 0 TO 4 AND Q IS AN INTEGER HAVING A VALUE OF FROM 1 TO 4 AND WHEREIN THE DOUBLE BOND OF SUCH BICYCLOALKENYL IS IN THE M, N, P, OR Q BRIDGE; R4 is hydrogen or methyl or together with R2 or R3 forms a cycloalkyl or bicycloalkyl or bicycloalkenyl as defined above, or together with R5 is a methylene chain of 3 to 5 carbon atoms such that a cycloalkyl of 4 to 6 carbon atoms inclusive is formed; R5 is selected from the group consisting of hydrogen, straight-chain alkyl having from 1 to 3 carbon atoms or together with R4 forms a cycloalkyl as defined above; and R6 is hydrogen or straight-chain alkyl having from 1 to 3 carbon atoms are disclosed. Pge1 ester analogues of the above formula, limited to the structures wherein two of R2, R3 R4 and R5 form a cycloalkyl, lower alkylated cycloalkyl, bicycloalkyl or bicycloalkenyl are also disclosed. The prostaglandin analogues selectively produce bronchodilation and decrease gastric secretion in vivo. Methods of preparing the analogues and starting materials required in the synthesis of the analogues are also disclosed.
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