Amidino

D, J Sturzebecher and WBode 1991. Geometry of Binding of the N-Alpha-Tosylated Piperidides of weffl-Amidino-Phenylalanine, Para Amidino-Phenylalanine and para-Guanidino-Phenylalanine to Thrombin and Trypsin - X-ray Crystal Structures of Their Trypsin Complexes and Modeling of their Thrombin Complexes. FEBS Letters 287 133-138. 

Many. groups such as carhoxamido, carboalkoxy, amidino, etc. are rather readily decomposed by nucleophiles. Some, such as nitrile and aldehyde groups, add nucleophiles reversibly (cf. 96). 

Carboxyl-related and acyl substituents. Included here are cyano, protonated amidinium ion, thionoacyl, acyl (Ar—CO, H—CO, Alkyl—CO), carboxamido, carboaryloxy, carboalkoxy, carboxy (unionized), amidino (unionized), and carboxylate anion, listed approximately in order of decreasing electron attraction or activation. The relative activation by some of these groups (e.g., ketone, aldehyde, nitrile) will change upon reversible interaction with the nucleophile, which will vary with the group and with the nucleophile (e.g., MeO , N3, NCS ). Irreversible interaction will be obvious when the reaction products in kinetic studies are characterized. 

Alteration of positional selectivity will result from built-in solvation of the transition state by an adjacent carboxyl-related function.Aminations will be so affected by carboxyl, carboxylate ion, carboalkoxy and less so by carboxamido groups (cf. Section I,D,2,b, structure 12.) Other substitutions such as alkoxylations can be so affected by carboxamido and amidino groups (cf. Section I,D, 2,b, structure 14). The effect of the cyclic hydrogen-bonded form (63) of 2-carboxamidopyridine on the reactivity of a leaving group is not known. 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

Intramolecular Cyelization of 3-(l-amidino-, 1-thioureido-, or 4-thiosemicarbazido)-4-oxo- or 4-thioxopyrimidines... 

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

Chemical Name N -[(4,5-dimethyl-2-oxazolyl)amidino] sulfanilamide Common Name Sulfadimethyloxazolylguanidine... 

Scheme 10.30 Part of clavulanic acid biosynthesis. Bonds installed byclavaminic acid synthase (CAS) are circled. CAS clavaminic acid synthase. PAH proclavaminic acid amidino hydrolase.

Cyclohexanedione (316) and ethyl 2-amidino-2-aminoacetate (317) (as hydrochloride) gave ethyl 3-amino-5,6,7,8-tetrahydro-2-quinoxalinecarboxy-late (318) (HjO-EtOH, AcONa, 10°C, 5 h %). ... 

C12H27AIO3 556-91-2) see Calusterone l-amidino-4-butyrylhomopiperazine (C ()H2oN40 59775-30-3) see Bunazosin... 

The products of these reactions, II and III, contain Hg—Rh and Hg—Ir bonds that are bridged by triazenide (II) and amidino (III) groups. 

After hybridization and washing, the samples were stained with DAPI (4, 6-di-amidino-2-phenylindole), which apparently associates in the minor groove of double-stranded DNA (Kapuscinski 1990). DAPI from Sigma was used. Binding of DAPI to double-stranded DNA occurs with about a 20-fold fluorescence enhancement, which usually does not occur with single-stranded DNA (Haugland 1992). 

The iminophosphoranes (181) with imide bromides gave the amidino-phosphonium bromides (183) which, it appears from their temperature-variable n.m.r. spectra, are interesting fluxional molecules. The free energy of activation for the interconversion of (183a) and (183b) (R R = Pr R3 = Ph) is 17.2 0.9kcalmol-i. 

Primarily using isolated plasma membrane vesicles as an experimental preparation, the functional properties of Na /H exchangers have been elucidated. The important kinetic properties include (1) stoichiometry (one-for-one) (2) reversibility (3) substrate specificity (monovalent cations Na, H, Li, NH4, but not K, Rb, Cs, choline) (4) modes of operation (Na -for-H, Na -for-Na Li " -for-Na, Na -for-NH4 ) (5) existence of an internal site for allosteric activation by (6) reversible inhibition by amiloride (Af-amidino-5-amino-6-chloropyr-azine carboxamide) and its 5-amino-substituted analogs and (7) competitive nature... 

Kamm, W., Hauptmann, J., Behrens, I., Sturzebecher, J., Dullweber, F., Gohlke, H., Stubbs, M., Klebe, G., Kissel, T., Transport of peptido-mimetic thrombin inhibitors with a 3-amidino-phenylalanine structure permeability and efflux mechanism in monolayers of a human intestinal cell line (Caco-2), Pharm. Res. 2001, 18, 1110-1118. 

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