- Why we might be misusing process mass intensity (PMI) and a methodology to apply it effectively as a discovery level metric
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Process mass intensity (PMI) is a key mass-based metric to evaluate the green credentials of an individual or sequence of reactions during process and chemical development. The increasing awareness to consider greenness as early as the initial discovery level, requires a set of parameters suitable to assess it at this stage of development, and guidelines to apply them correctly. This paper evaluates when and how PMI can be used in a correct manner. Different simulations for key reactions in the organic synthesis toolbox-i.e. amide bond formation and Mitsunobu reactions-illustrate that PMI can easily be misleading without due consideration of yield, concentration and molecular weight of reactants and product. A fair appraisal of the green potential of different methodologies therefore requires careful analysis of the examples and metrics data generated.
- Monteith, Edward R.,Mampuys, Pieter,Summerton, Louise,Clark, James H.,Maes, Bert U. W.,McElroy, C. Robert
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- PREPARATION AND UTILITY OF SUBSTITUTED QUINAZOLINE COMPOUNDS WITH ALPHA-ADRENERGIC BLOCKING EFFECTS
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The present disclosure is directed to modulators of alpha-adrenergic receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the use of such compounds for the treatment and/or management of hypertension, cardiac failure, prostatitis, and benign prostatic hyperplasia, and any other condition in which it is beneficial to modulate an alpha-adrenergic receptor.
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Page/Page column 71
(2008/06/13)
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- Molecular features of the prazosin molecule required for activation of Transport-P
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Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.
- da Silva, Joaquim Fernando Mendes,Walters, Marcus,Al-Damluji, Saad,Ganellin, C. Robin
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p. 7254 - 7263
(2008/12/23)
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- Direct synthesis of N-acylalkylenediamines from carboxylic acids under mild conditions
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Monoacylated piperazine derivatives were prepared directly from carboxylic acids and piperazine using triphenylphosphine (TPP) and N-bromosuccinimide (NBS) in dichloromethane. Inexpensive and readily available reagents, excellent yields, short reaction times and mild reaction conditions are important features of this method.
- Bandgar,Bettigeri
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p. 2917 - 2924
(2007/10/03)
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- Process for preparing amides
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The present invention provides a process for preparing an amide, which comprises reacting an amine with an ester in a molten form in the absence of a solvent.
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- Preparation of amides and quinazoline derivatives
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The present invention relates to a process for the preparation of amides, comprising reacting amines with carboxylic acids in the presence of silicon amines. The present invention further relates to a process for the preparation of quinazoline derivatives, comprising reacting amines with carboxylic acids in the presence of silicon amines to obtain amides and contacting the resultant amides with quinazoline.
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- Use of alpha-1C specific compounds to treat benign prostatic hyperplasia
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PCT No. PCT/US93/10950 Sec. 371 Date Apr. 1, 1997 Sec. 102(e) Date Apr. 1, 1997 PCT Filed Nov. 12, 1993 PCT Pub. No. WO94/10989 PCT Pub. Date May 26, 1994A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human alpha 1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human alpha 1A adrenergic receptor, a human alpha 1B adrenergic receptor, and a human histamine H1 receptor, and, binds to a human alpha 2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such alpha 1C adrenergic receptor. Compounds meeting these criteria are provided.
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- ALPHA1C SPECIFIC COMPOUNDS TO TREAT BENIGN PROSTATIC HYPERPLASIA
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This invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of an α 1C antagonist which (a) binds to a human α 1C adrenergic receptor with a binding affinity greater than 100-fold higher than the binding affinity with which the α 1C antagonist binds to a human α 1A adrenergic receptor, a human α 1B adrenergic receptor, and a human histamine H 1 receptor; and (b) binds to a human α 2 adrenergic receptor with a binding affinity which is greater than 100-fold lower than the binding affinity with which the α 1C antagonist binds to such α 1C adrenergic receptor.The invention further provides a method of inhibiting contraction of a prostate tissue which comprises contacting the prostate tissue with an effective contraction-inhibiting amount of an α 1C antagonist which (a) binds to a human α 1C adrenergic receptor with a binding affinity greater than 100-fold higher than the binding affinity with which the α 1C antagonist binds to a human α 1A adrenergic receptor, a human α 1B adrenergic receptor, and a human histamine H 1 receptor; and (b) binds to a human α 2 adrenergic receptor with a binding affinity which is greater than 100-fold lower than the binding affinity with which the α 1C antagonist binds to such α 1C adrenergic receptor.
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- DNA ENDODING HUMAN ALPHA 1 ADRENERGIC RECEPTORS
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This invention provides an isolated nucleic acid, vectors, transformed mammalian cells and non-human transgenic animals that encode and express normal or mutant alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention also provides a protein, and an antibody directed to the protein and pharmaceutical compounds related to alpha 1a, alpha 1b and alpha 1c adrenergic receptors. This invention provides nucleic acid probes, and antisense oligonucleotides complementary to alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and treatments for alleviating abnormalities associated with human alpha 1a, alpha 1b and alpha 1c adrenergic receptors.
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- HMDS-promoted in situ amidation reactions of carboxylic acids and amines
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A number of N-acylalkylenediamines were synthesized in high yields by in situ monoamidation of carboxylic acids with diamines. The amidation reactions were carried out simply by heating the substrates at 110 °C for 5-24 h in the presence of HMDS.
- Chou, Wen-Chih,Chou, Ming-Chen,Lu, Yann-Yu,Chen, Shyh-Fong
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p. 3419 - 3422
(2007/10/03)
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- Process for the manufacture of intermediates suitable to make doxazosin, terazosin, prazosin, tiodazosin and related antihypertensive medicines
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A process is provided for the manufacture of: where R is: STR1 comprising reacting: STR2 wherein R1 may be selected from H, Methyl, Ethyl and suitable lower alkyl groups, Cn H2n+1 (where n is from 3 to 5) or any other suitable group and thereafter if desired converting the resultant product to a salt thereof.
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- Aromatic amine derivatives
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This invention relates to novel aromatic amine compounds having the structure: STR1 where each W, Z1 and Z2 is independently H, C1 -C6 alkyl, C1 -C6 alkoxy, OH, F, Cl, Br, I, NO2, CN, SO2 NHR3, NR42, CONR32, COR5 ; where each R1 and R2 is independently H, C1 -C6 straight or branched chain alkyl or phenyl; where each X and Y is independently CH2, NR4, S, S=O, SO2 ; where n is 0, 1 or 2; where each p and q is independently 1 or 2; where R3 is H, C1 -C6 straight or branched chain alkyl or phenyl; where R4 is H, C1 -C6 straight or branched chain alkyl or COR3 ; and where R5 is H, C1 -C6 straight or branched chain alkyl or phenyl, C1 -C6 straight or branched chain alkoxy or OH. In addition the invention includes using such compounds for the treatment of benign prostatic hyperplasia, lowering intraocular pressure and inhibiting cholesterol synthesis.
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- USE OF ALPHA-1C SPECIFIC COMPOUNDS TO TREAT BENIGN PROSTATIC HYPERPLASIA
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The subject invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human . alpha. 1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human α 1A adrenergic receptor, a human α 1B adrenergic receptor, a human histamine H 1 receptor and α 2 adrenergic receptor. The subject invention also provides a method of inhibiting contraction of prostate tissue which comprises contacting the prostate tissue with an effective contraction-inhibiting amount of such compound.
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- Use of α1C specific compounds to treat benign prostatic hyperlasia
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A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human α1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human α1A adrenergic receptor, a human α1B adrenergic receptor, and a human histamine H1 receptor, and, binds to a human α2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such α1C adrenergic receptor. Compounds meeting these criteria are provided.
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- N-(2-benzimidazolyl)-piperazines
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Disclosed are compounds of the formula STR1 wherein n is 2 or 3, R is hydrogen or methyl, R' is C1 -C6 alkyl, acyl, aryl, aroyl, alkoxycarbonyl, tetrahydrofuroyl, dialkylaminocarbonyl, or furoyl, and R" is hydrogen and methoxy. These compounds are useful as antihypertensive agents.
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- Antihypertensive agents
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Described are antihypertensive agents selected from the class consisting of 2[4(tetrahydro-2-furoyl)-piperazino]-4-amino-6,7-dimethoxyquinazoline and 2-[4(tetrahydropyran-2-carbonyl)-piperazinyl]-4-amino-6,7-dimethoxyquinazoline, and pharmaceutically acceptable acid addition salts thereof. The compounds are highly water soluble and can be administered in time release form as well as parenterally, including intravenously.
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