# Patent

## Title
MAO-B inhibitors useful for treating obesity

## Abstract

The invention provides novel compounds of formulae I and II:




that are monoamine oxidase-B inhibitors, which can be useful in treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the priority benefit of U.S. Provisional Application No. 60/696,067 filed Jul. 1, 2005, which is incorporated herein by reference.


FIELD OF THE INVENTION
The present invention provides compounds and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).
BACKGROUND OF THE INVENTION
L-Selegiline is a monoamine oxidase (MAO) inhibitor that was developed for the treatment of neurological disorders and is primarily used to treat Parkinson's disease. MAO is an enzyme responsible for metabolizing biogenic monoamines including serotonin, dopamine, histamine, and phenylethylamine. By inhibiting MAO located in the central nervous system (CNS), MAO inhibitors and their analogues increase the concentration of monoamines present within the brain synapses. This enhances monoamine-mediated neurotransmission, effectively treating neurological disorders such as Parkinson's disease and depression.
MAO enzymes are also located in a number of peripheral (non-CNS) tissues, including adipose tissue, muscle, and liver. The function of MAO enzymes in these tissues has not been established. Currently, the only approved clinical use of L-selegiline and other MAO inhibitors is for the treatment of neurological disorders such as Parkinson's disease and depression.
Obesity is associated with an increase in the overall amount of adipose tissue (i.e., body fat), especially adipose tissue localized in the abdominal area. Obesity has reached epidemic proportions in the United States. The prevalence of obesity has steadily increased over the years among all racial and ethnic groups. According to the United States Surgeon General, 61% of the adult population and 14% of children are obese or overweight. Forty four million Americans are obese, with an additional eighty million deemed medically overweight. Obesity is responsible for more than 300,000 deaths annually, and will soon overtake tobacco usage as the primary cause of preventable death in the United States. Obesity is a chronic disease that contributes directly to numerous dangerous co-morbidities, including type 2 diabetes, cardiovascular disease, inflammatory diseases, premature aging, and some forms of cancer. Type 2 diabetes, a serious and life-threatening disorder with growing prevalence in both adult and childhood populations, is currently the 7th leading cause of death in the United States. Since more than 80% of patients with type 2 diabetes are overweight, obesity is the greatest risk factor for developing type 2 diabetes. Increasing clinical evidence indicates that the best way to control type 2 diabetes is to reduce weight.
The most popular over-the counter drugs for the treatment of obesity, phenylpropanolamine and ephedrine, and the most popular prescription drug, fenfluramine, were removed from the marketplace as a result of safety concerns. Drugs currently approved for the long-term treatment of obesity fall into two categories: (a) CNS appetite suppressants such as sibutramine and (b) gut lipase inhibitors such as orlistat. CNS appetite suppressants reduce eating behavior through activation of the ‘satiety center’ in the brain and/or by inhibition of the ‘hunger center’ in the brain. Gut lipase inhibitors reduce the absorption of dietary fat from the gastrointestinal (GI) tract. Although sibutramine and orlistat work through very different mechanisms, they share in common the same overall goal of reducing body weight secondary to reducing the amount of calories that reach the systemic circulation. Unfortunately, these indirect therapies produce only a modest initial weight loss (approximately 5% compared to placebo) that is usually not maintained. After one or two years of treatment, most patients return to or exceed their starting weight. In addition, most approved anti-obesity therapeutics produce undesirable and often dangerous side effects that can complicate treatment and interfere with a patient's quality of life.
The lack of therapeutic effectiveness, coupled with the spiraling obesity epidemic, positions the ‘treatment of obesity’ as one of the largest and most urgent unmet medical needs. There is, therefore, a real and continuing need for the development of improved medications that treat obesity.
MAO-B inhibitors such as selegiline have been clinically useful in the treatment of CNS disorders. They have now unexpectedly been discovered to also have anti-obesity activity. Even more surprising is that the anti-obesity activity effects of MAO-B inhibitors are mediated via a peripheral (i.e., non-CNS) mechanism. This new discovery provides a novel approach for the treatment of obesity. Moreover, if the CNS effects of these compounds can be reduced, their peripherally mediated anti-obesity properties should provide therapeutic agents with greater safety. It has, as a result, become highly desirable to find MAO-B inhibitors with limited or no CNS effects. Compounds of this sort are expected to be useful in treating obesity and the variety of co-morbidities to which it contributes.
SUMMARY OF THE INVENTION
Accordingly, in an aspect, the present invention provides novel MAO-B inhibitors or stereoisomers or pharmaceutically acceptable salts that are useful to treat obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).
In another aspect, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another aspect, the present invention provides novel methods for treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance), comprising: administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another aspect, the present invention provides novel methods for treating CNS disorders, comprising: administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another aspect, the present invention provides processes for preparing novel compounds.
In another aspect, the present invention provides novel compounds or stereoisomers or pharmaceutically acceptable salts for use in therapy.
In another aspect, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of obesity, diabetes, and/or cardiometabolic disorders.
In another aspect, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of CNS disorders.
These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that the presently claimed compounds or stereoisomers or pharmaceutically acceptable salts thereof are expected to be effective MAO-B inhibitors.


DETAILED DESCRIPTION OF THE INVENTION
The present invention is based on the unexpected finding that an MAO-B inhibitor is capable of reducing the amount of adipose tissue (i.e., body fat) in a warm-blooded mammal. This finding was unexpected because body fat can be reduced despite little, if any, concomitant reduction in food intake.
[1] In an embodiment, the present invention provides novel compound A or a stereoisomer or pharmaceutically acceptable salt thereof:




wherein: Y is O or H2 and R, R1, R2, X, X1, and Z are all independently selected from H, C1-6 alkyl, and a group capable of reducing or limiting the CNS activity of compound A; and,
provided that at least one of R, R1, R2, X, X1, and Z is other than H.
[2] In another embodiment, the present invention provides a novel compound of formula I or TI, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
R1 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)mCO2R, C2-6 alkenyl-CO2R, CH2CH(NHAc)CO2R, CH2CH(NHR)CO2R, and, (CH2)nPO(OR)2;
R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)mCO2R, C2-6 alkenyl-CO2R, (CH2)nCON(R)2, (CH2)nPO(OR)2, and (CH2)n-tetrazole;
X and X1 are independently selected from H, OR, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halogen, CF3, nitro, N(R)2, (CH2)m-tetrazole, (CH2)mCO2R, (CH2)mCONR2, (CH2)mCN, O(CH2)nCN, O(CH2)n-tetrazole, O(CH2)nCO2R, O(CH2)nCON(R)2, O—C2-6 alkenyl-CO2R, O(CH2)nPO(OR)2, NR—C2-4 alkenyl, NRSO2CH3, NR(CH2)nCO2R, NR(CH2)nCON(R)2, NR—C2-4 alkenyl-CO2R, NR(CH2)nPO(OR)2, NR(CH2)nSO2OR, NR(CH2)n-tetrazole, NRCO(CH2)nCO2R, NRCO(CH2)nCON(R)2, SO2NRCH3, OCH2CHMCONRCH2CO2R, CH2-aryl, O(CH2)nPO(OR)2, O(CH2)nSO2OR, (CH2)nN+(R)3A−, OCH2(CH2)nN+(R)3A−, O(CH2)n-biphenyl, O(CH2)n-biphenyl-(CH2)mCO2R, O(CH2)n-biphenyl-(CH2)mtetrazole, O(CH2)n-biphenyl-(CH2)mCN, O(CH2)n-biphenyl-(CH2)mCON(R)2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-(CH2)mCO2R, NR(CH2)n-biphenyl-(CH2)mtetrazole, NR(CH2)n-biphenyl-(CH2)mCN, NR(CH2)n-biphenyl-(CH2)mCON(R)2, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl(CH2)mCO2R, O(CH2)n-aryl-C2-6 alkenyl-CO2R, O(CH2)n-aryl(CH2)m-tetrazole, O(CH2)n-aryl(CH2)mCN, O(CH2)n-aryl(CH2)mCON(R)2, O(CH2)n-aryl(CH2)m—PO(OR)2, O(CH2)n-aryl-O(CH2)nCO2R, O(CH2)n-aryl-O—C2-6 alkenyl-CO2R, O(CH2)n-arylO(CH2)n-tetrazole, O(CH2)n-arylO(CH2)nCN, O(CH2)n-arylO(CH2)nCON(R)2, O(CH2)n-arylO(CH2), —PO(OR)2, O(CH2)n-aryl-NR(CH2)nCO2R, O(CH2)n-aryl-NRC2-6 alkenyl-CO2R, O(CH2)n-aryl-NR(CH2)n-tetrazole, O(CH2)n-aryl-NR(CH2)nCN, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)n—PO(OR)2, NR(CH2)n-aryl(CH2)mCO2R, NR(CH2)n-aryl-C2-6 alkenyl-CO2R, NR(CH2)n-aryl(CH2)m-tetrazole, NR(CH2)n-aryl(CH2)mCN, NR(CH2)n-aryl(CH2)mCON(R)2, NR(CH2)n-aryl(CH2)m—PO(OR)2, NR(CH2)n-aryl-NR(CH2)nCO2R, NR(CH2)n-aryl-NR—C2-6 alkenyl-CO2R, NR(CH2)n-aryl-NR(CH2)n-tetrazole, NR(CH2)n-aryl-NR(CH2)nCN, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nPO(OR)2, NR(CH2)n-arylO(CH2)nCO2R, NR(CH2)n-aryl-O—C2-6 alkenyl-CO2R, NR(CH2)n-aryl-O(CH2)n-tetrazole, NR(CH2)n-arylO(CH2)nCN, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-arylO(CH2)nPO(OR)2, O(CH2)n-heteroaryl(CH2)mCO2R, O(CH2)n-heteroaryl-C2-6 alkenyl-CO2R, O(CH2)n-heteroaryl(CH2)m-tetrazole, O(CH2)n-heteroaryl-(CH2)mCN, O(CH2)n-heteroaryl(CH2)mCON(R)2, O(CH2)n-heteroaryl(CH2)m—PO(OR)2, O(CH2)n-heteroaryl-O(CH2)nCO2R, O(CH2)n-heteroaryl-O—C2-6 alkenyl-CO2R, O(CH2)n-heteroarylO(CH2)n-tetrazole, O(CH2)n-heteroaryl O(CH2)nCN, O(CH2)n-heteroarylO(CH2)nCON(R)2, O(CH2)n-heteroarylO(CH2)n—PO(OR)2, O(CH2)n-heteroaryl-NR(CH2)nCO2R, O(CH2)n-heteroaryl-NR—C2-6 alkenyl-CO2R, O(CH2)n-heteroaryl-NR(CH2)n-tetrazole, O(CH2)n-heteroaryl-NR(CH2)nCN, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2), —PO(OR)2, NR(CH2)n-heteroaryl(CH2)mCO2R, NR(CH2)n-heteroaryl-C2-6 alkenyl-CO2R, NR(CH2)n-heteroaryl(CH2)m-tetrazole, NR(CH2)n-heteroaryl(CH2)mCN, NR(CH2)n-heteroaryl(CH2)mCON(R)2, NR(CH2)n-heteroaryl(CH2)m—PO(OR)2, NR(CH2)n-heteroaryl-NR(CH2)nCO2R, NR(CH2)n-heteroaryl-NR—C2-6 alkenyl-CO2R, NR(CH2)n-heteroaryl-NR(CH2)n-tetrazole, NR(CH2)n heteroaryl-NR(CH2)nCN, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nPO(OR)2, NR(CH2)n-heteroaryl-O(CH2)nCO2R, NR(CH2)n-heteroaryl-O—C2-6 alkenyl-CO2R, NR(CH2)n-heteroaryl-O(CH2)n-tetrazole, NR(CH2)n-heteroaryl-O(CH2)nCN, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroarylO(CH2)nPO(OR)2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2 and tetrazole is substituted with 0-1 R;
R3 is selected from H, C1-6 alkyl, and aryl-C1-6 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl;
A−, at each occurrence, is a counterion;
Y is selected from O and H2;
Z is selected from H, OR, O(CH2)nCO2R, O(CH2)nCONH2, OCH2CHMCONRCH2CO2R, OCH2CH(NHC(O)CH3)CO2R, OCH2CH(NHR)CO2R, O(CH2)nPO(OR)2, O(CH2)nSO2OR, O(CH2)n-tetrazole, O—C2-6 alkenyl, O(CH2)n-aryl, OCH2CH2CONRCH(OR)CO2R, OCH2CH2CONRC(R)2CH2SO2OR, NRR, NR(CH2)nCO2R, NR(CH2)nCONH2, NRCH2CHMCONRCH2CO2R, NRSO2R, NRCH2CH(NHC(O)CH3)CO2R, NRCH2CH(NHR)CO2R, NR(CH2)nPO(OR)2, NR(CH2)nSO2OR, NR(CH2)n-tetrazole, NR—C2-6 alkenyl, NR(CH2)n-aryl, NRCH2CH2CONRCH(OR)CO2R, NRCH2CH2CONRC(R)2CH2SO2OR, and NRCO(CH2)nCO2R, O(CH2)n-aryl-CO2R, O(CH2)n-aryl-tetrazole, O(CH2)n-aryl-CON(R)2, O(CH2)n-aryl-PO(OR)2, NR(CH2)n-aryl-CO2R, NR(CH2)n-aryl-tetrazole, NR(CH2)n-aryl-CON(R)2, and NR(CH2)n-aryl-PO(OR)2, wherein aryl is substituted with 1-2 X2 and tetrazole is substituted with 0-1 R;
when Y is H2, Z1 is selected from H, OR, O(CH2)nCO2R, O(CH2)nCONH2, OCH2CHMCONRCH2CO2R, OCH2CH(NHC(O)CH3)CO2R, OCH2CH(NHR)CO2R, O(CH2)nPO(OR)2, O(CH2)nSO2OR, O—C2-6 alkenyl, O(CH2)n-aryl, NR(CH2)n-aryl, OCH2CH2CONRCH(OR)CO2R, OCH2CH2CONRC(R)2CH2SO2OR, and NRCO(CH2)nCO2R, wherein aryl is substituted with 1-2 X2;
when Y is O, Z1 is selected from OR, NRR, NR(CH2)nCONH2, NR—C2-6 alkyl O(CH2)n-aryl, and NR(CH2)n-aryl, wherein aryl is substituted with 1-2 X2;
M is selected from H, C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, 5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, (CH2)n-aryl, and (CH2)n-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X2;
Q is selected from O−, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)n-aryl, and (CH2)n-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X2;
provided that when Q is other than O−, then A− is present;
m is selected from 0, 1, 2, 3, and 4;
n is selected from 1, 2, 3, and 4;
p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; and,
provided that in formula I:
(a) R is other than H and CH3,
(b) C(═Y)Z is other than CH3; and/or
(c) at least one of R1, R2, X, and X1 is other than H;
further provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
In another variant, the compounds of the present invention have no more than one acid functionality.
[3] In another embodiment, the present invention provides a novel compound of formula Ia, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-4 alkyl;
R1 is selected from H and C1-4 alkyl;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRSO2CH3, NRCO(CH2)nCON(R)2, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CON(R)2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, and NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2,
R3 is selected from H, C1-4 alkyl, and aryl-C1-14 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl; and,
provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[3a] In another embodiment, the present invention provides a novel compound of formula Ia, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CON(R)2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, and NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2.
[4] In another embodiment, the present invention provides a novel compound of formula Ib, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-4 alkyl;
R1 is selected from (CH2)mCO2R, C2-4 alkenyl-CO2R, CH2CH(NHAc)CO2R, CH2CH(NHR)CO2R, and, (CH2)nPO(OR)2;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)CON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-H(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)nbiphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2;
R3 is selected from H, C1-4 alkyl, and aryl-C1-4 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl;
M is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, (CH2)n-aryl, and (CH2)n-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X2; and,
provided that in formula Ib:
(a) R is other than H and CH3, and/or
(b) at least one of R1, X, and X1 is other than H;
further provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[4a] In another embodiment, the present invention provides a novel compound of formula Ib, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2.
[5] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-4 alkyl;
R1 is selected from H and C1-4 alkyl;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2;
R3 is selected from H, C1-4 alkyl, and aryl-C1-4 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl;
A− is selected from Cl− and Br−;
Z is selected from O(CH2)nCO2R, O(CH2)nCONH2, O(CH2)nPO(OR)2, O(CH2)nSO2OR, O(CH2)n-tetrazole, NR(CH2)nCO2R, NR(CH2)nCONH2, NRCH2CHMCONRCH2CO2R, NRSO2R, NR(CH2)nPO(OR)2, NR(CH2)nSO2OR, NR(CH2)n-tetrazole, NRCO(CH2)nCO2R, O(CH2)n-phenyl-CO2R, O(CH2)n-phenyl-tetrazole, O(CH2)n-phenyl-CON(R)2, O(CH2)n-phenyl-PO3(R)2, NR(CH2)n-phenyl-CO2R, NR(CH2)n-phenyl-tetrazole, NR(CH2)n-phenyl-CON(R)2, and NR(CH2)n-phenyl-PO3(R)2, wherein phenyl is substituted with 1-2 X2 and tetrazole is substituted with 0-1 R; and,
M is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, (CH2)n-aryl, and (CH2)n-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X2; and,
provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[5a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2.
[6] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-4 alkyl;
R1 is selected from H, C1-4 alkyl, (CH2)mCO2R, C2-4 alkenyl-CO2R, CH2CH(NHAc)CO2R, CH2CH(NHR)CO2R, and, (CH2)nPO(OR)2;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, N(R)2, (CH2)m-tetrazole, (CH2)mCO2R, (CH2)mCONR2, (CH2)mCN, O(CH2)nCN, O(CH2)n-tetrazole, O(CH2)nCO2R, O(CH2)nCON(R)2, O—C2-4 alkenyl-CO2R, O(CH2)nPO(OR)2, NR—C2-4 alkenyl, NRSO2CH3, NR(CH2)nCO2R, NR(CH2)nCON(R)2, NR—C2-4 alkenyl-CO2R, NR(CH2)nPO(OR)2, NR(CH2)nSO2OR, NR(CH2)n-tetrazole, NRCO(CH2)nCO2R, NRCO(CH2)nCON(R)2, SO2NRCH3, OCH2CHMCONRCH2CO2R, CH2-aryl, O(CH2)nPO(OR)2, O(CH2)nSO2R, (CH2)nN+(R)3A−, OCH2(CH2)nN+(R)3A−, O(CH2)n-biphenyl, O(CH2)n-biphenyl-(CH2)mCO2R, O(CH2)n-biphenyl-(CH2)mtetrazole, O(CH2)n-biphenyl-(CH2)mCN, O(CH2)n-biphenyl-(CH2)mCON(R)2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-(CH2)mCO2R, NR(CH2)n-biphenyl-(CH2)mtetrazole, NR(CH2)n-biphenyl-(CH2)mCN, NR(CH2)n-biphenyl-(CH2)mCON(R)2, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl(CH2)mCO2R, O(CH2)n-aryl-C2-4 alkenyl-CO2R, O(CH2)n-aryl(CH2)m-tetrazole, O(CH2)n-aryl(CH2)mCN, O(CH2)n-aryl(CH2)mCON(R)2, O(CH2)n-aryl(CH2)m—PO(OR)2, O(CH2)n-aryl-O(CH2)nCO2R, O(CH2)n-aryl-O—C2-4 alkenyl-CO2R, O(CH2)n-arylO(CH2)n-tetrazole, O(CH2)n-arylO(CH2)nCN, O(CH2)n-arylO(CH2)nCON(R)2, O(CH2)n-arylO(CH2), —PO(OR)2, O(CH2)n-aryl-NR(CH2)nCO2R, O(CH2)n-aryl-NRC2-4 alkenyl-CO2R, O(CH2)n-aryl-NR(CH2)n-tetrazole, O(CH2)n-aryl-NR(CH2)nCN, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)n—PO(OR)2, NR(CH2)n-aryl(CH2)mCO2R, NR(CH2)n-aryl-C2-4 alkenyl-CO2R, NR(CH2)n-aryl(CH2)m-tetrazole, NR(CH2)n-aryl(CH2)mCN, NR(CH2)n-aryl(CH2)mCON(R)2, NR(CH2)n-aryl(CH2)m—PO(OR)2, NR(CH2)n-aryl-NR(CH2)nCO2R, NR(CH2)n-aryl-NR—C2-4 alkenyl-CO2R, NR(CH2)n-aryl-NR(CH2)n-tetrazole, NR(CH2)n-aryl-NR(CH2)nCN, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nPO(OR)2, NR(CH2)n-arylO(CH2)nCO2R, NR(CH2)n-aryl-O—C2-4 alkenyl-CO2R, NR(CH2)n-aryl-O(CH2)n-tetrazole, NR(CH2)n-arylO(CH2)nCN, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-arylO(CH2)nPO(OR)2, O(CH2)n-heteroaryl(CH2)mCO2R, O(CH2)n-heteroaryl-C2-4 alkenyl-CO2R, O(CH2)n-heteroaryl(CH2)m-tetrazole, O(CH2)n-heteroaryl-(CH2)mCN, O(CH2)n-heteroaryl(CH2)mCON(R)2, O(CH2)n-heteroaryl(CH2)m—PO(OR)2, O(CH2)n-heteroaryl-O(CH2)nCO2R, O(CH2)n-heteroaryl-O—C2-4 alkenyl-CO2R, O(CH2)n-heteroarylO(CH2)n-tetrazole, O(CH2)n-heteroaryl O(CH2)nCN, O(CH2)n-heteroarylO(CH2)nCON(R)2, O(CH2)n-heteroarylO(CH2)n—PO(OR)2, O(CH2)n-heteroaryl-NR(CH2)nCO2R, O(CH2)n-heteroaryl-NR—C2-4 alkenyl-CO2R, O(CH2)n-heteroaryl-NR(CH2)n-tetrazole, O(CH2)n-heteroaryl-NR(CH2)nCN, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2), —PO(OR)2, NR(CH2)n-heteroaryl(CH2)mCO2R, NR(CH2)n-heteroaryl-C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl(CH2)m-tetrazole, NR(CH2)n-heteroaryl(CH2)mCN, NR(CH2)n-heteroaryl(CH2)mCON(R)2, NR(CH2)n-heteroaryl(CH2)m—PO(OR)2, NR(CH2)n-heteroaryl-NR(CH2)nCO2R, NR(CH2)n-heteroaryl-NR—C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl-NR(CH2)n-tetrazole, NR(CH2)n heteroaryl-NR(CH2)nCN, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nPO(OR)2, NR(CH2)n-heteroaryl-O(CH2)nCO2R, NR(CH2)n-heteroaryl-O—C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl-O(CH2)n-tetrazole, NR(CH2)n-heteroaryl-O(CH2)nCN, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroarylO(CH2)nPO(OR)2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2 and tetrazole is substituted with 0-1 R;
R3 is selected from H, C1-4 alkyl, and aryl-C1-4 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl;
A−, at each occurrence, is selected from Cl− and Br−;
Z is selected from H, OH, halogen, CF3, C1-4 alkoxy, O—C2-4 alkenyl, O(CH2)nCONH2, OCH2-aryl, NRR, NR—C2-4 alkenyl, NR(CH2)nCONH2, NR(CH2)n-aryl, and NRCO(CH2)nCO2R, wherein aryl is substituted with 1-2 X2;
M is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, (CH2)n-aryl, and (CH2)n-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and, wherein aryl and heteroaryl are substituted with 1-2 X2; and,
provided that in formula Ic:
(a) R is other than H and CH3,
(b) Z is other than H; and/or
(c) at least one of R1, X, and X1 is other than H;
further provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[6a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, N(R)2, (CH2)m-tetrazole, (CH2)mCO2R, (CH2)mCONR2, (CH2)mCN, O(CH2)nCN, O(CH2)n-tetrazole, O(CH2)nCO2R, O(CH2)nCON(R)2, O—C2-4 alkenyl-CO2R, O(CH2)nPO(OR)2, NR—C2-4 alkenyl, NRSO2CH3, NR(CH2)nCO2R, NR(CH2)nCON(R)2, NR—C2-4 alkenyl-CO2R, NR(CH2)nPO(OR)2, NR(CH2)nSO2OR, NR(CH2)n-tetrazole, NRCO(CH2)nCO2R, NRCO(CH2)nCON(R)2, SO2NRCH3, OCH2CHMCONRCH2CO2R, CH2-aryl, O(CH2)nPO(OR)2, O(CH2)nSO2OR, (CH2)nN+(CH3)3A−, OCH2(CH2)nN+(CH3)3A−, O(CH2)n-biphenyl, O(CH2)n-biphenyl-(CH2)mCO2R, O(CH2)n-biphenyl-(CH2)mtetrazole, O(CH2)n-biphenyl-(CH2)mCN, O(CH2)n-biphenyl-(CH2)mCON(R)2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-(CH2)mCO2R, NR(CH2)n-biphenyl-(CH2)mtetrazole, NR(CH2)n-biphenyl-(CH2)mCN, NR(CH2)n-biphenyl-(CH2)mCON(R)2, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl(CH2)mCO2R, O(CH2)n-aryl-C2-4 alkenyl-CO2R, O(CH2)n-aryl(CH2)m-tetrazole, O(CH2)n-aryl(CH2)mCN, O(CH2)n-aryl(CH2)mCON(R)2, O(CH2)n-aryl(CH2)m—PO(OR)2, O(CH2)n-aryl-O(CH2)nCO2R, O(CH2)n-aryl-O—C2-4 alkenyl-CO2R, O(CH2)n-arylO(CH2)n-tetrazole, O(CH2)n-arylO(CH2)nCN, O(CH2)n-arylO(CH2)nCON(R)2, O(CH2)n-arylO(CH2), —PO(OR)2, O(CH2)n-aryl-NR(CH2)nCO2R, O(CH2)n-aryl-NRC2-4 alkenyl-CO2R, O(CH2)n-aryl-NR(CH2)n-tetrazole, O(CH2)n-aryl-NR(CH2)nCN, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)n—PO(OR)2, NR(CH2)n-aryl(CH2)mCO2R, NR(CH2)n-aryl-C2-4 alkenyl-CO2R, NR(CH2)n-aryl(CH2)m-tetrazole, NR(CH2)n-aryl(CH2)mCN, NR(CH2)n-aryl(CH2)mCON(R)2, NR(CH2)n-aryl(CH2)m—PO(OR)2, NR(CH2)n-aryl-NR(CH2)nCO2R, NR(CH2)n-aryl-NR—C2-4 alkenyl-CO2R, NR(CH2)n-aryl-NR(CH2)n-tetrazole, NR(CH2)n-aryl-NR(CH2)nCN, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nPO(OR)2, NR(CH2)n-arylO(CH2)nCO2R, NR(CH2)n-aryl-O—C2-4 alkenyl-CO2R, NR(CH2)n-aryl-O(CH2)n-tetrazole, NR(CH2)n-arylO(CH2)nCN, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-arylO(CH2)nPO(OR)2, O(CH2)n-heteroaryl(CH2)mCO2R, O(CH2)n-heteroaryl-C2-4 alkenyl-CO2R, O(CH2)n-heteroaryl(CH2)m-tetrazole, O(CH2)n-heteroaryl-(CH2)mCN, O(CH2)n-heteroaryl(CH2)mCON(R)2, O(CH2)n-heteroaryl(CH2)m—PO(OR)2, O(CH2)n-heteroaryl-O(CH2)nCO2R, O(CH2)n-heteroaryl-O—C2-4 alkenyl-CO2R, O(CH2)n-heteroarylO(CH2)n-tetrazole, O(CH2)n-heteroaryl O(CH2)nCN, O(CH2)n-heteroarylO(CH2)nCON(R)2, O(CH2)n-heteroarylO(CH2)n—PO(OR)2, O(CH2)n-heteroaryl-NR(CH2)nCO2R, O(CH2)n-heteroaryl-NR—C2-4 alkenyl-CO2R, O(CH2)n-heteroaryl-NR(CH2)n-tetrazole, O(CH2)n-heteroaryl-NR(CH2)nCN, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)n—PO(OR)2, NR(CH2)n-heteroaryl(CH2)mCO2R, NR(CH2)n-heteroaryl-C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl(CH2)m-tetrazole, NR(CH2)n-heteroaryl(CH2)mCN, NR(CH2)n-heteroaryl(CH2)mCON(R)2, NR(CH2)n-heteroaryl(CH2)m—PO(OR)2, NR(CH2)n-heteroaryl-NR(CH2)nCO2R, NR(CH2)n-heteroaryl-NR—C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl-NR(CH2)n-tetrazole, NR(CH2)n heteroaryl-NR(CH2)nCN, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nPO(OR)2, NR(CH2)n-heteroaryl-O(CH2)nCO2R, NR(CH2)n-heteroaryl-O—C2-4 alkenyl-CO2R, NR(CH2)n-heteroaryl-O(CH2)n-tetrazole, NR(CH2)n-heteroaryl-O(CH2)nCN, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroarylO(CH2)nPO(OR)2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2 and tetrazole is substituted with 0-1 R.
[7] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-4 alkyl;
R1 is selected from H and C1-4 alkyl;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)CON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2;
R3 is selected from H, C1-4 alkyl, and aryl-C1-4 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl; and,
Z is selected from H, OH, C1-4 alkoxy, O—C2-4 alkenyl, O(CH2)nCONH2, OCH2-aryl, NRR, NR—C2-4 alkenyl, NR(CH2)nCONH2, and NRCH2-aryl, wherein aryl is substituted with 1-2 X2; and,
provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[7a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, N(R)2, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2N(C1-4 alkyl)2, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-(CH2)nCON(R)2, O(CH2)n-aryl-NR(CH2)nCON(R)2, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)N-heteroaryl-NR(CH2)nCON(R)2, NR(CH2)n-aryl-(CH2)mCON(R)2, NR(CH2)n-aryl-O(CH2)nCON(R)2, NR(CH2)n-aryl-NR(CH2)nCON(R)2, NR(CH2)n-heteroaryl-O(CH2)nCON(R)2, NR(CH2)n-heteroaryl-(CH2)mCON(R)2, NR(CH2)n-heteroaryl-NR(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)b-biphenyl, NR(CH2)n-biphenyl-CN, NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2.
[8] In another embodiment, the present invention provides a novel compound of formula IIa, or a stereoisomer or a pharmaceutically acceptable salt thereof:




wherein:
R, at each occurrence, is independently selected from H and C1-6 alkyl;
R1 is selected from H and C1-4 alkyl;
R2 is selected from H and C1-4 alkyl;
X and X1 are independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl; O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, and NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2;
R3 is selected from H, C1-4 alkyl, and aryl-C1-4 alkyl-;
X2, at each occurrence, is independently selected from H, OR, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halogen, CF3, nitro, —CN, C(O)NR2, NRSO2CH3, and SO2N(R)C1-4alkyl;
Y is selected from O and H2;
when Y is H2, Z1 is selected from H and OR;
when Y is O, Z1 is selected from NRR, NR(CH2)nCONH2, NR—C2-4 alkenyl, and NR(CH2)n-aryl, wherein aryl is substituted with 1-2 X2;
Q is selected from O−, C1-4 alkyl, C3-4 alkenyl, and C3-4 alkynyl; and,
provided that when Q is other than O−, A− is present and is selected from Cl and Br;
further provided that at least one of X and X1 is other than H, alkyl, alkoxy, hydroxy, and halo.
[8a] In another embodiment, the present invention provides a novel compound of formula IIa, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
one of X and X1 is H and the other selected from C2-4 alkenyl, C2-4 alkynyl, CF3, nitro, O(CH2)nCON(R)2, O—C2-4 alkenyl, (CH2)mCONR2, (CH2)mCN, NRCO(CH2)nCON(R)2, NRSO2CH3, SO2NRCH3, CH2-aryl, CH2-heteroaryl, O(CH2)n-aryl, O(CH2)n-heteroaryl, NR(CH2)n-aryl, NR(CH2)n-heteroaryl, O(CH2)n-aryl-(CH2)mCON(R)2, O(CH2)n-aryl-O(CH2)nCON(R)2, O(CH2)n-aryl, O(CH2)n-heteroaryl-(CH2)mCON(R)2, O(CH2)n-heteroaryl-O(CH2)nCON(R)2, O(CH2)n-biphenyl, O(CH2)n-biphenyl-CN, O(CH2)n-biphenyl-CONH2, NR(CH2)n-biphenyl, NR(CH2)n-biphenyl-CN, and NR(CH2)n-biphenyl-CONH2, and O(CH2CH2O)pCH2CH2OR3, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X2.
In another embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another embodiment, the present invention provides a novel method for treating a disease, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the disease is selected from obesity, diabetes, cardiometabolic disorders, and a combination thereof.
In another embodiment, the cardiometabolic disorder is selected from hypertension, dyslipidemias (e.g., undesirable blood lipid levels, elevated cholesterol levels, and lowered LDL levels), high blood pressure, and insulin resistance.
In another embodiment, the present invention provides a novel method for treating a co-morbidity of obesity, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another embodiment, the present invention provides a novel method for treating a co-morbidity of obesity, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another embodiment, the co-morbidity is selected from diabetes, Metabolic Syndrome, dementia, and heart disease.
In another embodiment, the co-morbidity is selected from hypertension; gallbladder disease; gastrointestinal disorders; menstrual irregularities; degenerative arthritis; venous statis ulcers; pulmonary hypoventilation syndrome; sleep apnea; snoring; coronary artery disease; arterial sclerotic disease; pseudotumor cerebri; accident proneness; increased risks with surgeries; osteoarthritis; high cholesterol; and, increased incidence of malignancies of the ovaries, cervix, uterus, breasts, prostrate, and gallbladder.
In another embodiment, the present invention provides a novel method for treating a CNS disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.
In another embodiment, the CNS disorder is selected from acute and chronic neurological disorders, cognitive disorders, and memory deficits. Examples of these disorders include chronic or traumatic degenerative processes of the nervous system, which include Alzheimer's disease, other types of dementia, minimal cognitive impairment, and Parkinson's disease. Other examples of CNS disorders include psychiatric diseases, which include depression, anxiety, panic attack, social phobia, schizophrenia, and anorexia. Further examples of CNS disorders include withdrawal syndromes induced by alcohol, nicotine and other addictive drugs. Additional examples of CNS disorders include neuropathic pain and neuroinflamatory diseases (e.g., multiple sclerosis).
In another embodiment, the present invention also provides a method of preventing or reversing the deposition of adipose tissue in a mammal by the administration of a MAO-B inhibitor. By preventing or reversing the deposition of adipose tissue, MAO-B inhibitors are expected to reduce the incidence or severity of obesity, thereby reducing the incidence or severity of associated co-morbidities.
In another embodiment, the present invention provides a compound of the present invention for use in therapy.
In another embodiment, the present invention provides the use of compounds of the present invention for the manufacture of a medicament for the treatment of obesity, diabetes, cardiometabolic disorders, and a combination thereof.
In another embodiment, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of CNS disorders.
The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. This invention encompasses all combinations of preferred aspects of the invention noted herein. It is understood that any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe additional more preferred embodiments. It is also to be understood that each individual element of the preferred embodiments is intended to be taken individually as its own independent preferred embodiment. Furthermore, any element of an embodiment is meant to be combined with any and all other elements from any embodiment to describe an additional embodiment.
Definitions
The examples provided in the definitions present in this application are non-inclusive unless otherwise stated. They include but are not limited to the recited examples.
The compounds herein described may have asymmetric centers, geometric centers (e.g., double bond), or both. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms, by synthesis from optically active starting materials, or through use of chiral auxiliaries. Geometric isomers of olefins, C═N double bonds, or other types of double bonds may be present in the compounds described herein, and all such stable isomers are included in the present invention. Specifically, cis and trans geometric isomers of the compounds of the present invention may also exist and may be isolated as a mixture of isomers or as separated isomeric forms. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. All tautomers of shown or described compounds are also considered to be part of the present invention.
The present invention includes all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.
Examples of the molecular weight of the compounds of the present invention include (a) less than about 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 grams per mole; (b) less than about 950 grams per mole; (c) less than about 850 grams per mole; and, (d) less than about 750 grams per mole.
“Alkyl” includes both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. C1-6 alkyl, for example, includes C1, C2, C3, C4, C5, and C6 alkyl groups. Examples of alkyl include methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl.
“Alkenyl” includes the specified number of hydrocarbon atoms in either straight or branched configuration with one or more unsaturated carbon-carbon bonds that may occur in any stable point along the chain, such as ethenyl and propenyl. C2-6 alkenyl includes C2, C3, C4, C5, and C6 alkenyl groups.
“Alkynyl” includes the specified number of hydrocarbon atoms in either straight or branched configuration with one or more triple carbon-carbon bonds that may occur in any stable point along the chain, such as ethynyl and propynyl. C2-6 Alkynyl includes C2, C3, C4, C5, and C6 alkynyl groups.
“Cycloalkyl” includes the specified number of hydrocarbon atoms in a saturated ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. C3-8 cycloalkyl includes C3, C4, C5, C6, C7, and C8 cycloalkyl groups.
“Alkoxy” represents an alkyl group as defined above with the indicated number of hydrocarbon atoms attached through an oxygen bridge. C1-6 alkoxy, includes C1, C2, C3, C4, C5, and C6 alkoxy groups. Examples of alkoxy include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy.
“Halo” or “halogen” refers to fluoro, chloro, bromo, and iodo.
“Counterion” is used to represent a small, negatively charged species, such as chloride, bromide, hydroxide, acetate, and sulfate.
“Aryl” refers to any stable 6, 7, 8, 9, 10, 11, 12, or 13 membered monocyclic, bicyclic, or tricyclic ring, wherein at least one ring, if more than one is present, is aromatic. Examples of aryl include fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.
“Heteroaryl” refers to any stable 5, 6, 7, 8, 9, 10, 11, or 12 membered monocyclic, bicyclic, or tricyclic heterocyclic ring that is aromatic, and which consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, O, and S. If the heteroaryl group is bicyclic or tricyclic, then at least one of the two or three rings must contain a heteroatom, though both or all three may each contain one or more heteroatoms. If the heteroaryl group is bicyclic or tricyclic, then only one of the rings must be aromatic. The N group may be N, NH, or N-substituent, depending on the chosen ring and if substituents are recited. The nitrogen and sulfur heteroatoms may optionally be oxidized (e.g., S, S(O), S(O)2, and N—O). The heteroaryl ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heteroaryl rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable.
Examples of heteroaryl includes acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, pteridinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.
Preventing the deposition of adipose tissue covers methods of treating wherein the levels of adipose tissue of a subject remain about the same as prior to being treated in accordance with the present invention (i.e., its pre-administration level) or not more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% greater than pre-administration level (particularly when the subject is pre-disposed to increasing adipose tissue levels).
Reversing the deposition of adipose tissue covers methods of treating wherein the levels of adipose tissue of a subject are lower than those prior to being treated in accordance with the present invention (i.e., its pre-administration level). Examples of lower include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20% or more lower than pre-administration level.
Mammal and patient covers warm blooded mammals that are typically under medical care (e.g., humans and domesticated animals). Examples of mammals include (a) feline, canine, equine, bovine, and human and (b) human.
“Treating” or “treatment” covers the treatment of a disease-state in a mammal, and includes: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, e.g., arresting it development; and/or (c) relieving the disease-state, e.g., causing regression of the disease state until a desired endpoint is reached. Treating also includes the amelioration of a symptom of a disease (e.g., lessen the pain or discomfort), wherein such amelioration may or may not be directly affecting the disease (e.g., cause, transmission, expression, etc.).
“Pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 1, 2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.
The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa., 1990, p 1445, the disclosure of which is hereby incorporated by reference.
“Therapeutically effective amount” includes an amount of a compound of the present invention that is effective when administered alone or in combination to treat obesity or another indication listed herein. “Therapeutically effective amount” also includes an amount of the combination of compounds claimed that is effective to treat the desired indication. The combination of compounds is preferably a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased effect, or some other beneficial effect of the combination compared with the individual components.
Utility
Obesity is defined as having a body mass index (BMI) of 30 or above. The index is a measure of an individual's body weight relative to height. BMI is calculated by dividing body weight (in kilograms) by height (in meters) squared. Normal and healthy body weight is defined as having a BMI between 20 and 24.9. Overweight is defined as having a BMI of 25 or above. Obesity has reached epidemic proportions in the U.S., with 44 million obese Americans, and an additional eighty million deemed medically overweight.
Obesity is a disease characterized as a condition resulting from the excess accumulation of adipose tissue, especially adipose tissue localized in the abdominal area. It is desirable to treat overweight or obese patients by reducing their amount of adipose tissue, and thereby reducing their overall body weight to within the normal range for their sex and height. In this way, their risk for co-morbidities such as diabetes and cardiovascular disease will be reduced. It is also desirable to prevent normal weight individuals from accumulating additional, excess adipose tissue, effectively maintaining their body weights at a BMI<25, and preventing the development of co-morbidities. It is also desirable to control obesity, effectively preventing overweight and obese individuals from accumulating additional, excess adipose tissue, reducing the risk of further exacerbating their co-morbidities.
There exist two forms of MAO, designated MAO-A and MAO-B. The two forms differ with respect to substrate and inhibitor specificities and amino acid number and sequence. A preferred substrate for MAO-B is beta-phenylethylamine. In contrast, a preferred substrate for MAO-A is serotonin. Some MAO inhibitors show selectivity for MAO-A or for MAO-B, whereas other MAO inhibitors show little, if any selectivity. For example, the MAO inhibitor clorgyline preferentially inhibits MAO-A; the MAO inhibitor L-selegiline preferentially inhibits MAO-B; and, the MAO inhibitor iproniazid is non-selective (i.e., has a similar affinity for both). Examples of selectivity include a compound having about 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or more fold higher affinity for one form of MAO than for the other form. One of ordinary skill in the art recognizes that there can be some difficulty in classifying MAO inhibitors. Some compounds may selectively inhibit one form of MAO in vitro and then lose their selectivity in vivo. Also, selectivity of a compound may vary from species to species or from tissue to tissue. In the context of the present invention, it is desirable to inhibit MAO-B activity in vivo in a mammal. Thus, selectivity and affinity are based on the in vivo activity of the MAO inhibitor and the mammalian species to which it is being or to be administered. Examples of the selectivity of a MAO-B inhibitor of the present invention include (a) at least a 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, to 100-fold greater affinity for MAO-B than MAO-A in the mammalian species (e.g., human) to be treated and (b) at least 100-fold greater affinity for MAO-B than MAO-A in the mammalian species (e.g., human) to be treated.
Some of the compounds of the present invention have been designed to have reduced CNS exposure by virtue of their inability or limited ability to penetrate the blood-brain barrier (e.g., quaternary salts or acid substituents) or by their participation in active transport systems, thus reducing centrally mediated side-effects, a potential problem with many anti-obesity agents.
Other compounds of the present invention are expected to penetrate the blood-brain barrier and therefore also be useful to treat CNS disorders (e.g., Parkinson's disease, depression, and Alzheimer's disease).
MAO enzymes are also located in a number of peripheral (non-CNS) tissues, including adipose tissue, muscle and liver. In order to treat non-CNS disorders (e.g., obesity, diabetes, and/or cardiometabolic disorders), it is necessary to administer enough of a drug sufficient to inhibit MAO in peripheral tissues. MAO inhibitors in use today to treat various psychiatric and neurological diseases, regardless of route of administration, enter the CNS from the systemic circulation. While present in the systemic circulation, such drugs have access to peripheral tissues, including adipose tissue, liver, and muscle. One of skill in the art recognizes that MAO inhibitors intended to enter the CNS from the systemic circulation in order to treat psychiatric and neurological diseases also have access to MAO in peripheral tissues, including adipose tissue, liver, and muscle. Thus, an MAO inhibitor useful for treating non-CNS disorders may have some access to the CNS from the systemic circulation.
Drugs enter the CNS from the systemic circulation by crossing the blood-brain barrier (BBB). The BBB is a highly specialized ‘gate-keeper’ that protects the brain by preventing the entry of many potentially harmful substances into the CNS from the systemic circulation. Much is known about the BBB, and of the physical-chemical properties required for compounds transported across it.
Drugs that do not cross the BBB into the CNS or that are readily eliminated through transport mechanisms (J Clin Invest. 97, 2517 (1996)) are known in the literature and have low CNS activity due to their inability to develop brain levels necessary for pharmacological action. The BBB has at least one mechanism to remove drugs prior to their accumulation in the CNS. P-Glycoproteins (P-gp) localized in plasma membrane of the BBB can influence the brain penetration and pharmacological activity of many drugs through translocation across membranes. The lack of accumulation into the brain by some drugs can be explained by their active removal from the brain by P-gp residing in the BBB. For example, the typical opioid drug loperamide, clinically used as an antidiarrheal, is actively removed from the brain by P-gp, thus explaining its lack of opiate-like CNS effects. Another example is domperidone, a dopamine receptor blocker that participates in the P-gp transport (J Clin Invest. 97, 2517 (1996)). Whereas dopamine receptor blockers that cross the BBB can be used to treat schizophrenia, the readily-eliminated domperidone can be used to prevent emesis, without the likelihood of producing adverse CNS effects.
In addition to the above compounds, agents possessing structural characteristics that retard or prevent BBB penetration or contribute to participation in active elimination processes have been identified in various classes of therapeutics. These include antihistamines (Drug Metab. Dispos. 31, 312 (2003)), beta-adrenergic receptor antagonists (B-blockers) (Eur. J. Clin. Pharmacol. 28, Suppl: 21-3 (1985); Br. J. Clin. Pharmacol., 11 (6), 549-553 (1981)), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (J. Pharm Sci., 88(10) 950-954 (1999)), and opioid antagonists. This latter group has been tested in relation to their activity in the GI tract. These peripherally selective opioid antagonists are described in various US patents as being useful in the treatment of non-CNS pathologies in mammals, in particular those of the GI tract (see U.S. Pat. No. 5,260,542; U.S. Pat. No. 5,434,171; U.S. Pat. No. 5,159,081; and U.S. Pat. No. 5,270,238).
Other types of non-brain penetrant compounds can be prepared through the creation of a charge within the molecule. Thus, the addition of a methyl group to the tertiary amine functionality of the drugs scopolamine or atropine, unlike the parent molecules, prevents their passage across the BBB through the presence of a positive charge. However, the new molecules (methyl-scopolamine and methyl-atropine) retain their full anticholinergic pharmacological properties. As such, these drugs can also be used to treat peripheral diseases, without the concern of adverse CNS effects. The quaternary ammonium compound methylnaltrexone is also used for the prevention and/or treatment of opioid and non-opioid induced side effects associated with opioid administration.
MAO-B inhibitors such as selegiline have been useful in the treatment of CNS disorders. The unexpected discovery that the anti-obesity activity mediated by these agents is mediated by a non-CNS mechanism may make it desirable that the compounds of the present invention be peripherally restricted, i.e., have an inability or limited ability to cross the BBB or be readily eliminated from the brain through active transport systems, when a non-CNS disorder is to be treated. It may be desirable for the compounds of the present invention to be peripherally restricted, which in turn will result in no or very limited CNS effects. Compounds that provide peripherally mediated anti-obesity properties should result in therapeutic agents with greater safety, as previously demonstrated in earlier classes of peripherally restricted agents. It can be desirable that the compounds of the present invention, when administered in a therapeutically effective amount, have no or very limited CNS effects. It can also be desirable that the lack of CNS effects is a result of the compounds of the present invention having minimal brain concentrations when administered in therapeutically effective amounts. In this context, minimal brain concentrations means levels that are too low to be therapeutically effective for the treatment of a CNS indication or too low to cause significant or measurable deleterious or undesired side effects. It is noted that CNS activity is desirable when seeking to treat a CNS disorder.
Compound A is Selegiline when Y is O and R, R1, R2, X, X1, and Z are all H. Selegiline is a drug that crosses the BBB and is indicated for the treatment of Parkinson's disease. In compound A, one of R, R1, R2, X, X1, and Z is a group capable of reducing or limiting the CNS activity of compound A. This reduced or limited CNS activity occurs via at least one of R, R1, R2, X, X1, and Z being a group that either limits compound A's ability to cross the BBB relative to that of Selegiline or enables it to be actively removed at a rate greater than that of Selegiline. Examples of brain levels of compound A include levels that are (a) from 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% lower than Selegiline, when administered at the same dosage; (b) from 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% lower than Selegiline, when administered at the same dosage; and, (c) from 98, 99, to 100% lower than Selegiline, when administered at the same dosage.
Most methods of treating obesity are dependent on a significant reduction in energy intake, either by a decrease in food intake (e.g., sibutramine) or by inhibition of fat absorption (e.g., orlistat). In the present invention, it can be desirable for adipose tissue to be significantly reduced in the absence of a significant reduction in food intake. The weight loss, as a result of the present invention, comes from the treatment with an MAO-B inhibitor, largely independent of appetite and food intake. Examples of the level of food intake during adipose tissue loss include (a) food intake is maintained, increased or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) food intake is maintained, increased, or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below its pre-administration level; (c) food intake is maintained, increased or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below its pre-administration level; and (d) food intake level is maintained, increased or about 0, 1, 2, 3, 4, or 5% below its pre-administration level.
In some cases, loss of adipose tissue can be accompanied by a concomitant loss of lean muscle mass. This is particularly evident in cancer patients who show a wasting of all body tissue components, including adipose tissue and lean muscle mass. In the present invention, however, it can be desirable for body fat to be significantly reduced in the absence of a significant reduction in lean body mass. Adipose tissue loss comes from treatment with an MAO-B inhibitor, independent of a significant change in lean body mass. Examples of the level of lean body mass during adipose tissue loss include (a) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below pre-administration levels; (c) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below pre-administration levels; and (d) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, or 5% below pre-administration levels.
In some cases, loss of adipose tissue can be accompanied by a concomitant loss of water mass. This is particularly evident with diet regimens that promote dehydration. In the present invention, it can be desirable for body fat to be significantly reduced in the absence of a significant reduction in water mass. In other words, adipose tissue loss comes from treatment with an MAO-B inhibitor, independent of a significant change in water mass. Examples of the level of water mass during adipose tissue loss include (a) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below pre-administration levels; (c) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below pre-administration levels; and (d) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, or 5% below pre-administration levels.
Sibutramine and orlistat are currently marketed for use in the treatment of obesity. These two compounds achieve weight loss through entirely different mechanisms. Sibutramine, a CNS appetite suppressant, inhibits the neuronal reuptake of serotonin and noradrenaline. Orlistat inhibits gut lipase enzymes that are responsible for breaking down ingested fat.
The mechanism of action of MAO-B inhibitors is believed to be entirely different from appetite suppressants, gut lipase inhibitors, and other agents with similar indications (e.g., serotonin agonists, leptin, and fatty acid synthase inhibitors). Co-administration of a MAO-B inhibitor together with one or more other agents that are useful for treating the indications described above (e.g., obesity, diabetes, cardiometabolic disorders, and a combination thereof) is expected to be beneficial, by producing, for example, either additive or synergistic effects. Examples of additional agents include an appetite suppressant and a lipase inhibitor. Therefore, the present invention provides a method of treating obesity, diabetes, and/or cardiometabolic disorders, comprising administering a therapeutically effective amount of a compound of the present invention and a second component selected from an appetite suppressant (e.g., sibutramine, phentermine, fenfluramine) and a gut lipase inhibitor (e.g., orlistat).
MAO-B inhibitors are expected to promote weight loss without appreciably reducing caloric intake. Co-administration of an MAO-B inhibitor together with an appetite suppressant is expected to produce either additive or synergistic effects on weight loss. Similarly, co-administration of an MAO-B inhibitor together with a lipase inhibitor is expected to produce either additive or synergistic effects on weight loss.
The ability of compounds to inhibit MAOs can be determined using the method of R. Uebelhack et al., Pharmacopsychiatry 31, 187-192 (1988)(as described below).
Preparation of platelet-rich plasma and platelets. Venous blood from healthy subjects was collected between 8 and 8.30 a.m. after an overnight fast into EDTA-containing vacutainer tubes (11.6 mg EDTA/ml blood). After centrifugation of the blood at 250×g for 15 minutes at 20° C., the supernatant platelet-rich plasma (PRP) was collected and the number of platelets in PRP counted with a cell counter (MOIAB, Hilden, Germany). 2 ml of PRP was spun at 1500×g for 10 min to yield a platelet pellet. The pellet was washed three times with ice-cold saline, resuspended in 2 ml Soerensen phoshate buffer, pH 7.4 and stored at −18° C. for one day.
MAO assay. Fresh PRP or frozen platelet suspension (100 μL) was generally preincubated for 10 min in the absence or presence of drugs at 37° C. in 100 uL of 0.9% NaCl solution or phosphate buffer pH 7.4, respectively, at 37° C. 50 μL of 2-phenylethylamine-[ethyl-1-14C]hydrochloride (P EA) solution (specific activity 56 Ci/mol, Amersham) was then added in a final concentration of 5 μM, and the incubation was continued for 30 min. The reaction was terminated by the addition of 50 μL of 4M HClO4. The reaction product of MAO, phenylacetaldehyde, was extracted into 2 mL of n-hexane. An aliquot of the organic phase was added to scintillator cocktail and the radioactivity was determined using a liquid scintillation counter. Product formation was linear with time for at least 60 min with appropriate platelet numbers. Blank values were obtained by including 2 mM pargyline in the incubation mixtures. All assays were performed in duplicate.
The ability of compounds to inhibit MAO activity can also be determined using the following method. cDNA's encoding human MAO-B can be transiently transfected into EBNA cells using the procedure described by E.-J. Schlaeger and K. Christensen (Transient Gene Expression in Mammalian Cells Grown in Serum-free Suspension Culture; Cytotechnology, 15: 1-13, 1998). After transfection, cells are homogeneized by means of a Polytron homogeneiser in 20 mM Tris HCl buffer, pH 8.0, containing 0.5 mM EGTA and 0.5 mM phenylmethanesulfonyl fluoride. Cell membranes are obtained by centrifugation at 45,000×g and, after two rinsing steps with 20 mM Tris HCl buffer, pH 8.0, containing 0.5 mM EGTA, membranes are eventually re-suspended in buffer and aliquots stored at −80° C. until use.
MAO-B enzymatic activity can be assayed using a spectrophotometric assay adapted from the method described by M. Zhou and N. Panchuk-Voloshina (A One-Step Fluorometric Method for the Continuous Measurement of Monoamine Oxidase Activity, Analytical Biochemistry, 253: 169-174, 1997). Briefly, membrane aliquots are incubated in 0.1 M potassium phosphate buffer, pH 7.4, for 30 min at 37° C. with or without various concentrations of the compounds. After incubation, the enzymatic reaction is started by the addition of the MAO substrate tyramine together with 1 U/ml horse-radish peroxidase (Roche Biochemicals) and 80 μM N-acetyl-3,7,-dihydroxyphenoxazine (Amplex Red, Molecular Probes). The samples are further incubated for 30 min at 37° C. in a final volume of 200 μl and absorbance is determined at a wavelength of 570 nm using a SpectraMax plate reader (Molecular Devices). Background (non-specific) absorbance is determined in the presence of 10 μM L-deprenyl for MAO-B. IC50 values are determined from inhibition curves obtained using nine inhibitor concentrations in duplicate, by fitting data to a four parameter logistic equation.
Compounds of the present invention are expected to be MAO-B inhibitors. Representative compounds have been tested, as measured in the assay described herein, and have been shown to be active as their IC50 values were found to be in the range of ≦10 μM. Compounds of the present invention are considered to be MAO-B inhibitors if they have an IC50 value less than or equal to 10 μM. Additional examples of desirable activity levels of MAO-B inhibitors useful in the present invention include (a) an IC50 value of 1 μM or lower, (b) an IC50 value of 0.1 μM or lower, (c) an IC50 value of 0.01 μM or lower, (d) an IC50 value of 0.001 μM or lower, and (e) an IC50 value of 0.0001 μM or lower.
In the present invention, MAO-B inhibitor(s) can be administered enterally, parenterally, orally, and transdermally. One skilled in this art is aware that the routes of administering the compounds of the present invention may vary significantly. In addition to other oral administrations, sustained release compositions may be favored. Other examples of routes include injections (e.g., intravenous, intramuscular, and intraperitoneal); subcutaneous; subdermal implants; buccal, sublingual, topical (e.g., a dermal patch), rectal, vaginal, and intranasal administrations. Bioerodible, non-bioerodible, biodegradable, and non-biodegradable systems of administration may also be used.
If a solid composition in the form of tablets is prepared, the main active ingredient can be mixed with a pharmaceutical vehicle, examples of which include silica, starch, lactose, magnesium stearate, and talc. The tablets can be coated with sucrose or another appropriate substance or they can be treated so as to have a sustained or delayed activity and so as to release a predetermined amount of active ingredient continuously. Gelatin capsules can be obtained by mixing the active ingredient with a diluent and incorporating the resulting mixture into soft or hard gelatin capsules. A syrup or elixir can contain the active ingredient in conjunction with a sweetener, which is preferably calorie-free, an antiseptic (e.g., methylparaben and/or propylparaben), a flavoring, and an appropriate color. Water-dispersible powders or granules can contain the active ingredient mixed with dispersants or wetting agents or with suspending agents such as polyvinylpyrrolidone, as well as with sweeteners or taste correctors. Rectal administration can be effected using suppositories, which are prepared with binders melting at the rectal temperature (e.g., cocoa butter and/or polyethylene glycols). Parenteral administration can be effected using aqueous suspensions, isotonic saline solutions, or injectable sterile solutions, which contain pharmacologically compatible dispersants and/or wetting agents (e.g., propylene glycol and/or polyethylene glycol). The active ingredient can also be formulated as microcapsules or microspheres, optionally with one or more carriers or additives. The active ingredient can also be presented in the form of a complex with a cyclodextrin, for example α-, β-, or γ-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and/or methyl-β-cyclodextrin.
The dose of the MAO-B inhibitor administered daily will vary on an individual basis and to some extent may be determined by the severity of the disease being treated (e.g., obesity). The dose of the MAO-B inhibitor will also vary depending on the MAO-B inhibitor administered. An example of a range of dosages of an MAO-B inhibitor is about from 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 76, 80, 85, 90, 95, to 100 mg/kg of mammal body weight. The MAO-B inhibitor can be administered in a single dose or in a number of smaller doses over a period of time. The length of time during which the MAO-B inhibitor is administered varies on an individual basis, and can continue until the desired results are achieved (i.e., reduction of body fat, or prevention of a gain in body fat). Therapy could, therefore, last from 1 day to weeks, months, or even years depending upon the subject being treated, the desired results, and how quickly the subject responds to treatment in accordance with the present invention.
A possible example of a tablet of the present invention is as follows.














Ingredient
mg/Tablet



















Active ingredient
100



Powdered lactose
95



White corn starch
35



Polyvinylpyrrolidone
8



Na carboxymethylstarch
10



Magnesium stearate
2



Tablet weight
250










A possible example of a capsule of the present invention is as follows.














Ingredient
mg/Tablet



















Active ingredient
50



Crystalline lactose
60



Microcrystalline cellulose
34



Talc
5



Magnesium stearate
1



Capsule fill weight
150










In the above capsule, the active ingredient has a suitable particle size. The crystalline lactose and the microcrystalline cellulose are homogeneously mixed with one another, sieved, and thereafter the talc and magnesium stearate are admixed. The final mixture is filled into hard gelatin capsules of suitable size.
A possible example of an injection solution of the present invention is as follows.














Ingredient
mg/Tablet









Active substance
 1.0 mg



1 N HCl
20.0 μl



acetic acid
 0.5 mg



NaCl
 8.0 mg



Phenol
10.0 mg



1 N NaOH
q.s. ad pH 5



H2O
q.s. ad 1 mL










Synthesis

The compounds of the present invention can be prepared in a number of ways known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or by variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will be understood by those skilled in the art of organic synthesis that the functionality present on the molecule should be consistent with the transformations proposed. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1991). All references cited herein are hereby incorporated in their entirety herein by reference.




Scheme 1 provides access to one of a series of compounds that are part of the present invention. An amino acid ester, such as phenylalanine (X=H) or O-benzyltyrosine (X=O-benzyl), can be N-alkylated using formalin and sodium cyanoborohydride in the presence of acetic acid to provide an N-methylated ester (step a). Alternatively, alkylation of the amino ester with propargyl bromide in DMF at about 50° C. in the presence potassium carbonate should give the monopropargyl amino ester which can be converted to the des-methyl acid of the compound described in step e, below. When the secondary amine is treated with propargyl bromide in DMF in the presence of potassium carbonate at about 50° C., the tertiary amino ester will be produced (step b). Hydrolysis of the ester using aqueous LiOH solution in a co-solvent should afford the desired amino acid (step c). If the tertiary amino ester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid (step d) prior to hydolysis of the ester (step e).
Alternatively, if the tertiary amino ester is reduced with lithium aluminum hydride (LAH), the primary alcohol will be produced (step f). Deprotonation of the alcohol with sodium hydride followed by alkylation with ethyl bromopropionate will afford the amino alkoxyester (step g). Treatment of this ester as in step c will yield the tertiary amino acid (step h). If the tertiary amino alkoxyester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid prior to hydolysis of the ester.




Scheme 2 illustrates how one could make susbstituted propargyl compounds of the present invention. A starting propargyl amine can be deprotonated with n-butyl lithium at low temperature in a solvent such as THF, and the resulting anion alkylated with methylchloroformate or ethyl bromoacetate to afford an aminoester (step a). Hydrolysis of the ester using aqueous LiOH in a co-solvent can afford an amino acid (step b). Alternatively, if the tertiary amino ester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid prior to hydrolysis of the ester.




Scheme 3 shows how to prepare hydroxy-phenyl and substituted hydroxyphenyl compounds of the present invention. A starting p-hydroxyphenethylamine can be treated with sodium hydide and the resulting phenoxide anion can be alkylated with ethyl bromoacetate to provide an ester (step a). The carboxylic acid can then be formed by the previously described hydrolysis (step b). If the alkoxide anion was alkylated with 1,3-dibromopropane, then a bromoalkylether should be produced (step c). This halide, in turn, could be treated with trimethyl amine to give the propyloxy-trimethyl ammonium salt (step d). Treatment of the hydroxyphenyl compound with formalin and dimethyl amine followed by further reaction with acetic anhydride and concentrated hydrochloric acid should yield the intermediate chloromethylated phenol (step e). Subsequent reaction with excess trimethylamine should afford the trimethylammonium salt (step f).




Scheme 4 describes the synthesis of optionally substituted benzyloxy compounds. This reaction scheme as well as the procedures found in J. Org. Chem. 1991, 56, 2395 can also be utilized to prepare substituted-biphenylmethyl analogs of this and the anilino compounds of Scheme 5 by utilizing commercially available 4′-bromomethylbiphenyl-2-carbonitrile, or for unsubstituted compounds commercially available 4-phenylbenzyl bromide, to alkylate the phenol of Scheme 4 and the anilines of Scheme 5, respectively. Treatment of the phenol with an optionally substituted benzyl bromide in a solvent such as acetone in the presence of a base such as potassium carbonate upon heating should afford the benzyl ether (step a). If the substituent on the benzyloxy group is an ester or a carbon-chain linked ester, the acid can be produced via hydrolysis using lithium hydroxide in aqueous THF (step b). If the benzyl bromide contains a nitrile subtituent or a alkyl-chain linked substituent with a nitrile group or an oxyalkyl-chain linked substituent with a nitrile group, the alkylation product (step c) can be treated with 30% hydrogen peroxide and potassium carbonate in DMSO to produce the amides (step d). Alternatively, if these nitriles are reacted with sodium azide in the presence of zinc chloride in aqueous solution or treated with trialkyltin chloride and sodium azide in refluxing toluene or xylene, followed by removal of the triakyl tin group with anhydrous HCl in THF/toluene, the tetrazoles should be formed (step e).




Scheme 5 describes the general synthesis of achiral compounds starting from substituted phenylacetones. If one uses commercially available 4-nitophenyl acetone, an anilino compound of step e that can also be used as a starting material for the reactions of Scheme 4, can be produced. Treatment of a nitro-phenyl acetone with benzylamine in the presence of sodium triacetoxyborohydride in dichloroethane (DCE) and acetic acid at 25-30° C. will yield the secondary amine (step a). Alkylation of the amine using formalin and sodium triacetoxyborohydride in DCE and HOAc at about 30° C. will provide the tertary amine (step b). Reduction of the nitro group using Fe and ammonium formate in methanol at reflux will afford the anilino compound that has also been debenzylated (step c). Alkylation of the secondary amine with propargylbromide in the presence of potassium carbonate in acetonitrile at room temperature can give the tertiary amine (step d). Treatment of this aniline with benzaldehydes in the presence of triacetoxyborohydride in DCE and HOAc will yield benzylated anilines with optionally selected substituents that can be used further for the transformations described in Scheme 4 (step e). Reaction of this aniline with methanesulfonyl chloride in the presence of a base will provide the sulfonamide derivative (step f). In addition, reaction of this aniline with acid chlorides such as ethyl malonyl chloride or 3-cyanobenzenesulfonyl chloride will produce the acetanilide or the sulfonamide, respectively.




Scheme 6 describes how one can form quarternary ammonium salts or N-oxides of the present invention. When a starting tertiary propargyl amine is treated with an alkyl halide such as propoargyl bromide in a solvent such as methanol or ethanol the quaternary ammonium salt can result (step a). Alternatively, a tertiary propargyl amine treated with an oxidizing agent such as 2-phenylsulfonyl-3-phenyloxaziridine (Davis reagent) in the presence of potassium carbonate in methylene chloride should give the amine N-oxides (step b).




Scheme 7 illustrates a route to another series of compounds that are part of the present invention. An amino acid ester, optionally substituted on the aromatic ring, can be N-alkylated using formalin and sodium cyanoborohydride under slightly acidic conditions to provide an N-methylated ester (step a). The secondary amine can then be alkylated with propargyl bromide to give a tertiary amino ester (step b). If the tertiary amino ester is reduced with lithium aluminum hydride (LAH), the primary alcohol should be produced (step c). Deprotonation of the alcohol with sodium hydride followed by alkylation with benzyl bromide should afford the amino benzyl ether (step d). Treatment of this ether with butyl lithium followed by ethyl bromoacetate should produce the acetylenic ester (step e). Hydrolysis of the ester using aqueous LiOH in a co-solvent will afford an amino acid (step f). The benzyl group can be removed using trifluoroacetic acid to give the amino acid alcohol (step g).




As shown in Scheme 8, the previously described amino alcohol (Scheme 1, step f) can be oxidized to the aldehyde using the Dess-Martin periodinane [1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one] in wet dichlormethane at about room temperature (step a). Treatment of the amino aldehyde with aqueous ammonia in the presence of sodium cyanoborohydride or with hydroxylamine followed by lithium aluminum hydride reduction should give the primary amine (step b). Reaction of the primary amine with methane sulfonyl chloride will afford the sulfonamide derivative (step c). The primary amine can also be reacted with ethyl 4-bromocrotonate in DMF in the presence of potassium carbonate to give the diaminoester (step d). Subsequent hydrolysis using lithium hydroxide in aqueous THF solution willl provide the diamino acid (step e). The primary amine can also be treated with ethyl malonyl chloride in the presence of pyridine to give the amide ester (step f). Subsequent treatment with lithium hydroxide in aqueous THF solution will provide the acid (step g).




Scheme 9 shows the synthesis of chiral analogs of selegiline starting from L-tyrosine methyl ester. Treatment of the ester with di-t-butyl-dicarbonate (t-Boc anhydride) in methanol in the presence of triethylamine at 40-50° C. will provide the N-t-BOC-protected ester (step a). The phenol can be alkylated with benzyl bromide or a substituted version thereof, in acetone at 50-60° C. for about 4 hours to yield the O-benzyl ether analogs (step b). The t-BOC group will then be removed with TFA in methylene chloride at room temperature for 18-20 hours (step c), and the ester can be reduced with LAH at about 60 degrees C. for 6-8 hours to afford the alcohol (step d). Protection of the amine with t-Boc anhydride in methanol in the presence of triethylamine at 40-50° C. provides the N-t-BOC-protected ester (step e). The alcohol can be converted to the iodide with iodine in the presence of triphenylphosphine and imidazole in dichloromethane at about 40-50° C. for 4-6 hours (step f). Reduction of the iodide is carried out using sodium borohydride in DMSO at about 90° C. for about 1 hour (step g). Removal of the t-BOC group with TFA in methylene chloride at room temperature for about 15-20 hours will give the amine (step h), and reductive amination using formalin, sodium triacetoxyborohydride, HOAc in dichloromethane for about 24 hours will afford the methylated amine (step i). Subsequent alkylation with propargyl bromide in the presence of potassium carbonate in acetone for about 20 hours will produce the teriary amine (step j). In Scheme 9, Bn is benzyl or benzyl optionally substituted with substituents that are compatible with LAH reduction. To produce substituted benzyl compounds with groups that are not compatible with LAH reduction, the product of step j (unsubstituted benzyl) can be de-benzylated with TFA, and the resulting phenol can be re-alkylated with benzyl halides containing various substituents on the phenyl ring.




As shown in Scheme 10, hydroxy-selegiline can be coupled with a polyethylene glycol (PEG), with one protected hydroxyl group (e.g., with a t-butyldimethylsilyl (TBDMS), alkyl, benzyl or aralkyl group), under Mitsunobu conditions using diethylazodicarboxylate (DEAD) and triphenylphosphine in a solvent (e.g., THF) to produce phenolethers (step a). The compounds with a terminal alkyl or aryl-alkyl group can be quaternized with an alkyl or propargyl halide in a variety of solvents (e.g., ether, ethanol, or toluene) to produce the quaternary ammonium salts (step b). The TBDMS-protected PEG pendants can be treated with tetrabutylammonium fluoride in THF to give the PEG pendants with terminal hydroxyl groups (step c). These alcohols can also be converted to the quaternary salts as described above (step d). The various mono-terminally substituted PEG-halides can be prepared by procedures described in Nuclear Medicine and Biology, 32, 799 (2005) or are commercially available.




Alternatively, as shown in Scheme 11, a hydroxyphenylacetic acid ester can be coupled with a halo-polyethylene glycol (PEG), optionally terminally substituted (e.g., TBDMS, alkyl, benzyl, or aryl-alkyl group), in DMF in the presence of potassium carbonate at about 100° C. with stirring for 12-16 hours to afford the PEG ether ester (step a). After hydrolysis of the ester with lithium hydroxide in aqueous THF, the resultant acid can converted to the acid chloride upon heating in oxalyl chloride (step b). Treatment of the acid chloride with 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) should produce the acylated anhydride (step c), and subsequent hydrolysis in aqueous acetic acid will provide the methyl ketone (step d). Reductive amination of the ketone with methylpropargylamine in the presence of sodium triacetoxyborohydride in dichloroethane and acetic acid should afford the amine (step e). The compounds with a terminal alkyl or aryl-alkyl group can be quaternized with alkyl or propargyl halides in a variety of solvents such as ether, ethanol, or toluene to produce the quaternary ammonium salts (step f). The TBDMS-protected PEG pendants can be treated with tetrabutylammonium fluoride in THF to give the PEG pendants with terminal hydroxyl groups (step g). These alcohols can also be converted to the quaternary salts as described above (step h).
One stereoisomer of a compound of the present invention may be a more potent MAO-B inhibitor than its counterpart(s). Thus, stereoisomers are included in the present invention. Some of these stereoisomers are shown below in Scheme 12. When required, separation of the racemic material can be achieved by HPLC using a chiral column or by a resolution using a resolving agent such as described in Wilen, S. H. Tables of Resolving Agents and Optical Resolutions 1972, 308 or using enantiomerically pure acids and bases. A chiral compound of the present invention may also be directly synthesized using a chiral catalyst or a chiral ligand, e.g., Jacobsen, E. Acc. Chem. Res. 2000, 33, 421-431 or using other enantio- and diastereo-selective reactions and reagents known to one skilled in the art of asymmetric synthesis.




Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments that are given for illustration of the invention and are not intended to be limiting thereof.
EXAMPLES
Tables A and B below describe examples of the present invention that have been prepared. The examples can be prepared according to the methods of the scheme numbers provided for each example.
For X, the number in the parentheses indicates the substituent's position on phenyl ring in the X group.







TABLE A













 
















NMR



Ex #
X
Y
Z
(Solvent)
Scheme















1
OCH2C6H5
H2
H
(CDCl3)
4,9






CH3: 0.97(d)







C≡CH: 2.25(m)







PhCH: 2.35(m)







NCH3: 2.43(s)







PhCH: 2.96(m)







NCH: 3.01(m)







NCH2: 3.44(m)







PhCH2O: 5.04(s)







aromatic H's 6.89-7.44



2
OCH2C6H4—
H2
H
(CDCl3)
4



CO2CH3(3)


CH3: 0.98(d)







C≡CH: 2.27(m)







PhCH: 2.36(m)







NCH3: 2.44(s)







PhCH: 2.93(m)







NCH: 3.00(m)







NCH2: 3.45(q)







OCH3: 3.93(s)







PhCH2O: 5.08(s)







aromatic H's 6.89-8.11



3
OCH2C6H4—
H2
H
(CDCl3)
4



CONH2(4)


CH3: 1.00(d)







C≡CH: 2.17(m)







PhCH: 2.30(m)







NCH3: 2.47(s)







PhCH: 3.00(m)







NCH: 3.00(m)







NCH2: 3.48(m)







OCH3: 3.92(s)







PhCH2O: 5.11(s)







aromatic H's 6.89, 7.10,







7.52, 7.84 d's



4
OCH2C6H4—
H2
H
(CD3OD)
4



CONH2(3)


CH3: 0.98(d)







PhCH: 2.34(m)







NCH3: 2.41(s)







C≡CH: 2.70(m)







PhCH: 3.00(m)







NCH: 3.00(m)







NCH2: 3.45(m)







PhCH2O: 5.12(s)







aromatic H's 6.93-7.97



5
OCH2CH═CH—
H2
H
(CDCl3)
3



CO2CH2CH3


CH3: 0.96(d)







ester-CH3: 1.30(t)







C≡CH: 2.25(m)







PhCH: 2.35(m)







NCH3: 2.42(s)







PhCH: 2.95(m)







NCH: 2.99(m)







NCH2: 3.43(q)







OCH2: 4.22(q)







OCH2vinyl: 4.68(m)







CH═: 6.19(dt)







CH═: 7.06(dt)







C6H4: 6.83, 7.09(dd)



6
OCH2C6H5
O
OCH3
(CDCl3)
1



N—CH3═N—H


C≡CH: 2.17(m)




in


PhCH2: 2.93(dq)




structure at top


NCH2: 3.39(dq)




of table


OCH3: 3.67(s)







NCH: 3.70(m)







PhCH2O: 5.03(s)







aromatic H's 6.89-7.40



7
OCH2C6H4—
H2
H
(CD3OD)
4



OCH2CONH2


CH3: 0.96(d)




(3)


PhCH: 2.35(m)







NCH3: 2.42(s)







C≡CH: 2.70(m)







PhCH: 2.99(m)







NCH2: 3.46(m)







PhCH2CO: 3.54(s)







PhCH2O: 5.05(s)







aromatic H's 6.90-7.41



8
OCH2C6H4—
H2
H
(CD3OD)
4



CH2CONH2(3)


CH3: 0.96(d)







PhCH: 2.33(m)







NCH3: 2.40(s)







C≡CH: 2.70(m)







PhCH: 3.00(m)







NCH2: 3.48(m)







OCH2CO: 4.50(s) 







PhCH2O: 5.04(s)







aromatic H's 6.90-7.33



9
H
H2
OH
(CDCl3)
1






C≡CH: 2.28(m)







NCH3: 2.42(s)







NCH, PhCH: 3.09(m)







NCH2, 3.38(m)







CH2O: 3.43(d)







aromatic H's 7.15-7.30



10
OCH2C6H5
H2
OH
(CDCl3)
1






C≡CH: 2.30(m)







PhCH: 2.35(t)







NCH3: 2.45(s)







PhCH: 3.01(m)







NCH: 3.04(m)







NCH2, 3.40(m)







CH2O: 3.47(d)







PhCH2O: 5.04(s)







aromatic H's 6.89-7.44



11
OCH2C6H5
O
OCH3
(CDCl3)
1






C≡CH: 2.27(m)







NCH3: 2.46(s)







PhCH2: 2.97(d)







NCH2: 3.50(dq)







OCH3: 3.57(s)







NCH: 3.58(m)







PhCH2O: 5.03(s)







aromatic H's 6.88-7.41



12
NO2
H2
H
(CDCl3)
5






CH3: 1.00(d)







C≡CH: 2.26(m)







PhCH: 2.58(m)







NCH3: 2.41(s)







PhCH: 3.05(m)







NCH: 3.05(m)







NCH2: 3.42(q)







aromatic H's: 7.34, 7.36,







8.14, 8.16



13
OCH2C6H4CH3
H2
H
(CDCl3)
4,9



(3)


CH3: 0.97(d)







C≡CH: 2.24(m)







PhCH: 2.36(m)







PhCH3: 2.37(s)







NCH3: 2.42(s)







PhCH: 2.97(m)







NCH: 3.05(m)







NCH2: 3.43(q)







PhCH2O: 5.00(s)







aromatic H's: 6.89-7.29



14
OCH2C6H4CF3
H2
H
(CDCl3)
4,9



(3)


CH3: 0.99(d)







C≡CH: 2.27(m)







PhCH: 2.38(m)







NCH3: 2.45(s)







PhCH: 2.97(m)







NCH: 3.00(m)







NCH2: 3.47(q)







PhCH2O: 5.09(s)







aromatic H's: 6.89-7.63



15
OCH2C6H4CH3
H2
H
(CDCl3)
4,9



(4)


CH3: 0.96(d)







C═CH: 2.24(m)







PhCH: 2.35(m)







PhCH3: 2.36(s)







NCH3: 2.42(s)







PhCH: 2.95(m)







NCH: 2.97(m)







NCH2: 3.42(q)







PhCH2O: 4.99(s)







aromatic H's: 6.88-7.32



16
OCH2C6H4CN
H2
H
(CDCl3)
4,9



(3)


CH3: 0.97(d)







C≡CH: 2.26(m)







PhCH: 2.38(m)







NCH3: 2.43(s)







PhCH: 2.97(m)







NCH: 2.99(m)







NCH2: 3.44(q)







PhCH2O: 5.07(s)







aromatic H's: 6.87-7.65



17
NHCH2C6H4CN
H2
H
(CDCl3)
5



(4)


CH3: 0.97(d)







C≡CH: 2.22(m)







PhCH: 2.27(m)







NCH3: 2.39(s)







PhCH: 2.86(m)







NCH: 2.91(m)







NCH2:3.40(g)







PhCH2N: 4.39(s)







aromatic H's: 6.50(d),







6.97(d), 7.47(d), 7.60(d)



18
NHCH2C6H4OH
H2
H
(CDCl3)
5



(4)


CH3: 0.96(d)







C≡CH: 2.24(m)







PhCH: 2.27(m)







NCH3: 2.42(s)







PhCH: 2.86(m)







NCH: 2.91(m)







NCH2: 3.43(q)







PhCH2N: 4.21(s)







aromatic H's: 6.57(d),







6.80(d), 6.97(d), 7.23(d)



19
NHCH2C6H4OH
H2
H
(CDCl3)
5



(3)


CH3: 0.95(d)







C≡CH: 2.23(m)







PhCH: 2.28(m)







NCH3: 2.41(s)







PhCH: 2.89(m)







NCH: 2.92(m)







NCH2: 3.42(q)







PhCH2N: 4.26(s)







aromatic H's: 6.53-7.20
















TABLE B













 
















NMR



Ex #
X
R
Q
(Solvent)
Scheme















1
H
CH3
CH2C≡CH
(CD3OD)
6






CH3(d) 1.40







NCH3(s) 3.30







CH(m) 4.20







NCH2(m) 4.70







C6H5: 7.33-7.44



2
OCH2C6H5
CH3
CH2C≡CH
(CD3OD)
6






CH3: 1.34(d)







PhCH: 2.74(t)







NCH3: 3.25 s







C≡CH: 3.30(m)







PhCH: 3.43(d)







CH: 4.07(m)







NCH2: 4.64(m)







PhCH2O: 5.08(s)







C6H4: 7.00, 7.21







(dd), C6H5:







7.30-7.44



3
OCH2C6H5
CH3
CH3
(CD3OD)
6






CH3: 1.30(d)







PhCH: 2.67(t)







NCH3: 3.22(s)







C≡CH: 3.30(m)







PhCH: 3.40(d)







CH: 3.90(m)







NCH2: 4.51(q)







PhCH2O: 5.07(s)







7.99, 7.21(dd)







C6H5: 7.27-7.43









Tables I-Xb show representative examples of the compounds of the present invention. Each example in each table represents an individual species of the present invention.







TABLE I













 











Ex. #
X
X1
R
R1














1
H
H
CH3
H


2
H
H
H
H


3
H
H
CH3
CH3


4
H
H
H
CH3


5
OH
H
CH3
H


6
OH
H
H
H


7
OH
H
CH3
CH3


8
OH
H
H
CH3


9
OCH3
H
CH3
H


10
OCH3
H
H
H


11
OCH3
H
CH3
CH3


12
OCH3
H
H
CH3


13
OCH2C6H5
H
CH3
H


14
OCH2C6H5
H
H
H


15
OCH2C6H5
H
CH3
CH3


16
OCH2C6H5
H
H
CH3


17
OCH2CH2C6H5
H
CH3
H


18
OCH2CH2C6H5
H
H
H


19
OCH2CH2C6H5
H
CH3
CH3


20
OCH2CH2C6H5
H
H
CH3


21
OCH2CH═CH2
H
CH3
H


22
OCH2CH═CH2
H
H
H


23
OCH2CH═CH2
H
CH3
CH3


24
OCH2CH═CH2
H
H
CH3


25
OCH2CONH2
H
CH3
H


26
OCH2CONH2
H
H
H


27
OCH2CONH2
H
CH3
CH3


28
OCH2CONH2
H
H
CH3


29
Cl
H
CH3
H


30
Cl
H
H
H


31
Cl
H
CH3
CH3


32
Cl
H
H
CH3


33
NO2
H
CH3
H


34
NO2
H
H
H


35
NO2
H
CH3
CH3


36
NO2
H
H
CH3


37
NH2
H
CH3
H


38
NH2
H
H
H


39
NH2
H
CH3
CH3


40
NH2
H
H
CH3


41
NHSO2CH3
H
CH3
H


42
NHSO2CH3
H
H
H


43
NHSO2CH3
H
CH3
CH3


44
NHSO2CH3
H
H
CH3


45
OH
CH2N(CH3)2
CH3
H


46
OH
CH2N(CH3)2
H
H


47
OH
CH2N(CH3)2
CH3
CH3


48
OH
CH2N(CH3)2
H
CH3


49
OH
CH2N−(CH3)3Cl−
CH3
H


50
OH
CH2N−(CH3)3Cl−
H
H


51
OH
CH2N−(CH3)3Cl−
CH3
CH3


52
OH
CH2N−(CH3)3Cl−
H
CH3


53
OCH3
CH2N(CH3)2
CH3
H


54
OCH3
CH2N(CH3)2
H
H


55
OCH3
CH2N(CH3)2
CH3
CH3


56
OCH3
CH2N(CH3)2
H
CH3


57
OCH3
CH2N−(CH3)3Cl−
CH3
H


58
OCH3
CH2N−(CH3)3Cl−
H
H


59
OCH3
CH2N−(CH3)3Cl−
CH3
CH3


60
OCH3
CH2N−(CH3)3Cl−
H
CH3
















TABLE II













 










Ex. #
X
X1
R1













1
H
H
CO2CH2CH3


2
H
H
CO2H


3
OH
H
CO2CH2CH3


4
OH
H
CO2H


5
OCH3
H
CO2CH2CH3


6
OCH3
H
CO2H


7
OCH2CH═CH2
H
CO2CH2CH3


8
OCH2CH═CH2
H
CO2H


9
OCH2C6H5
H
CO2CH2CH3


10
OCH2C6H5
H
CO2H


11
OCH2CH2C6H5
H
CO2CH2CH3


12
OCH2CH2C6H5
H
CO2H


13
OCH2CONH2
H
CO2CH2CH3


14
OCH2CONH2
H
CO2H


15
Cl
H
CO2CH2CH3


16
Cl
H
CO2H


17
NO2
H
CO2CH2CH3


18
NO2
H
CO2H


19
NH2
H
CO2CH2CH3


20
NH2
H
CO2H


21
NHSO2CH3
H
CO2CH2CH3


22
NHSO2CH3
H
CO2H


23
OH
CH2N(CH3)2
CO2CH2CH3


24
OH
CH2N(CH3)2
CO2H


25
OCH3
CH2N(CH3)2
CO2CH2CH3


26
OCH3
CH2N(CH3)2
CO2H


27
OCH2C6H5
CH2N(CH3)2
CO2CH2CH3


28
OCH2C6H5
CH2N(CH3)2
CO2H


29
OH
CH2N−(CH3)3Cl−
CO2CH2CH3


30
OH
CH2N−(CH3)3Cl−
CO2H


31
OCH3
CH2N−(CH3)3Cl−
CO2CH2CH3


32
OCH3
CH2N−(CH3)3Cl−
CO2H


33
OCH2C6H5
CH2N−(CH3)3Cl−
CO2CH2CH3


34
OCH2C6H5
CH2N−(CH3)3Cl−
CO2H


35
H
H
CH2CO2CH2CH3


36
H
H
CH2CO2H


37
OH
H
CH2CO2CH2CH3


38
OH
H
CH2CO2H


39
OCH3
H
CH2CO2CH2CH3


40
OCH3
H
CH2CO2H


41
OCH2CH═CH2
H
CH2CO2CH2CH3


42
OCH2CH═CH2
H
CH2CO2H


43
OCH2C6H5
H
CH2CO2CH2CH3


44
OCH2C6H5
H
CH2CO2H


45
OCH2CH2C6H5
H
CH2CO2CH2CH3


46
OCH2CH2C6H5
H
CH2CO2H


47
OCH2CONH2
H
CH2CO2CH2CH3


48
OCH2CONH2
H
CH2CO2H


49
Cl
H
CH2CO2CH2CH3


50
Cl
H
CH2CO2H


51
NO2
H
CH2CO2CH2CH3


52
NO2
H
CH2CO2H


53
NH2
H
CH2CO2CH2CH3


54
NH2
H
CH2CO2H


55
NHSO2CH3
H
CH2CO2CH2CH3


56
NHSO2CH3
H
CH2CO2H


57
OH
CH2N(CH3)2
CH2CO2CH2CH3


58
OH
CH2N(CH3)2
CH2CO2H


59
OCH3
CH2N(CH3)2
CH2CO2CH2CH3


60
OCH3
CH2N(CH3)2
CH2CO2H


61
OCH2C6H5
CH2N(CH3)2
CH2CO2CH2CH3


62
OCH2C6H5
CH2N(CH3)2
CH2CO2H


63
OH
CH2N−(CH3)3Cl−
CH2CO2CH2CH3


64
OH
CH2N−(CH3)3Cl−
CH2CO2H


65
OCH3
CH2N−(CH3)3Cl−
CH2CO2CH2CH3


66
OCH3
CH2N−(CH3)3Cl−
CH2CO2H


67
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CO2CH2CH3


68
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CO2H


69
H
H
CH2CH2CO2CH2CH3


70
H
H
CH2CH2CO2H


71
OH
H
CH2CH2CO2CH2CH3


72
OH
H
CH2CH2CO2H


73
OCH3
H
CH2CH2CO2CH2CH3


74
OCH3
H
CH2CH2CO2H


75
OCH2CH═CH2
H
CH2CH2CO2CH2CH3


76
OCH2CH═CH2
H
CH2CH2CO2H


77
OCH2C6H5
H
CH2CH2CO2CH2CH3


78
OCH2C6H5
H
CH2CH2CO2H


79
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3


80
OCH2CH2C6H5
H
CH2CH2CO2H


81
OCH2CONH2
H
CH2CH2CO2CH2CH3


82
OCH2CONH2
H
CH2CH2CO2H


83
Cl
H
CH2CH2CO2CH2CH3


84
Cl
H
CH2CH2CO2H


85
NO2
H
CH2CH2CO2CH2CH3


86
NO2
H
CH2CH2CO2H


87
NH2
H
CH2CH2CO2CH2CH3


88
NH2
H
CH2CH2CO2H


89
NHSO2CH3
H
CH2CH2CO2CH2CH3


90
NHSO2CH3
H
CH2CH2CO2H


91
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3


92
OH
CH2N(CH3)2
CH2CH2CO2H


93
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3


94
OCH3
CH2N(CH3)2
CH2CH2CO2H


95
OCH2C6H5
CH2N(CH3)2
CH2CH2CO2CH2CH3


96
OCH2C6H5
CH2N(CH3)2
CH2CH2CO2H


97
OH
CH2N−(CH3)3Cl−
CH2CH2CO2CH2CH3


98
OH
CH2N−(CH3)3Cl−
CH2CH2CO2H


99
OCH3
CH2N−(CH3)3Cl−
CH2CH2CO2CH2CH3


100
OCH3
CH2N−(CH3)3Cl−
CH2CH2CO2H


101
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH2CO2CH2CH3


102
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH2CO2H


103
H
H
CH2CH═CHCO2CH2CH3


104
H
H
CH2CH═CHCO2H


105
OH
H
CH2CH═CHCO2CH2CH3


106
OH
H
CH2CH═CHCO2H


107
OCH3
H
CH2CH═CHCO2CH2CH3


108
OCH3
H
CH2CH═CHCO2H


109
OCH2CH═CH2
H
CH2CH═CHCO2CH2CH3


110
OCH2CH═CH2
H
CH2CH═CHCO2H


111
OCH2C6H5
H
CH2CH═CHCO2CH2CH3


112
OCH2C6H5
H
CH2CH═CHCO2H


113
OCH2CH2C6H5
H
CH2CH═CHCO2CH2CH3


114
OCH2CH2C6H5
H
CH2CH═CHCO2H


115
OCH2CONH2
H
CH2CH═CHCO2CH2CH3


116
OCH2CONH2
H
CH2CH═CHCO2H


117
Cl
H
CH2CH═CHCO2CH2CH3


118
Cl
H
CH2CH═CHCO2H


119
NO2
H
CH2CH═CHCO2CH2CH3


120
NO2
H
CH2CH═CHCO2H


121
NH2
H
CH2CH═CHCO2CH2CH3


122
NH2
H
CH2CH═CHCO2H


123
NHSO2CH3
H
CH2CH═CHCO2CH2CH3


124
NHSO2CH3
H
CH2CH═CHCO2H


125
OH
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


126
OH
CH2N(CH3)2
CH2CH═CHCO2H


127
OCH3
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


128
OCH3
CH2N(CH3)2
CH2CH═CHCO2H


129
OCH2C6H5
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


130
OCH2C6H5
CH2N(CH3)2
CH2CH═CHCO2H


131
OH
CH2N−(CH3)3Cl−
CH2CH═CHCO2CH2CH3


132
OH
CH2N−(CH3)3Cl−
CH2CH═CHCO2H


133
OCH3
CH2N−(CH3)3Cl−
CH2CH═CHCO2CH2CH3


134
OCH3
CH2N−(CH3)3Cl−
CH2CH═CHCO2H


135
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH═CHCO2CH2CH3


136
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH═CHCO2H


137
H
H
CH2CH2PO(OCH2CH3)2


138
H
H
CH2CH2PO(OH)2


139
OH
H
CH2CH2PO(OCH2CH3)2


140
OH
H
CH2CH2PO(OH)2


141
OCH3
H
CH2CH2PO(OCH2CH3)2


142
OCH3
H
CH2CH2PO(OH)2


143
OCH2CH═CH2
H
CH2CH2PO(OCH2CH3)2


144
OCH2CH═CH2
H
CH2CH2PO(OH)2


145
OCH2C6H5
H
CH2CH2PO(OCH2CH3)2


146
OCH2C6H5
H
CH2CH2PO(OH)2


147
OCH2CH2C6H5
H
CH2CH2PO(OCH2CH3)2


148
OCH2CH2C6H5
H
CH2CH2PO(OH)2


149
OCH2CONH2
H
CH2CH2PO(OCH2CH3)2


150
OCH2CONH2
H
CH2CH2PO(OH)2


151
Cl
H
CH2CH2PO(OCH2CH3)2


152
Cl
H
CH2CH2PO(OH)2


153
NO2
H
CH2CH2PO(OCH2CH3)2


154
NO2
H
CH2CH2PO(OH)2


155
NH2
H
CH2CH2PO(OCH2CH3)2


156
NH2
H
CH2CH2PO(OH)2


157
NHSO2CH3
H
CH2CH2PO(OCH2CH3)2


158
NHSO2CH3
H
CH2CH2PO(OH)2


159
OH
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


160
OH
CH2N(CH3)2
CH2CH2PO(OH)2


161
OCH3
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


162
OCH3
CH2N(CH3)2
CH2CH2PO(OH)2


163
OCH2C6H5
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


164
OCH2C6H5
CH2N(CH3)2
CH2CH2PO(OH)2


165
OH
CH2N−(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


166
OH
CH2N−(CH3)3Cl−
CH2CH2PO(OH)2


167
OCH3
CH2N−(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


168
OCH3
CH2N−(CH3)3Cl−
CH2CH2PO(OH)2


169
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


170
OCH2C6H5
CH2N−(CH3)3Cl−
CH2CH2PO(OH)2
















TABLE IIIa













 











Ex. #
X
X1
Z1
R1














1
H
H
CH2CO2CH2CH3
H


2
H
H
CH2CO2H
H


3
H
H
CH2CO2CH2CH3
CH3


4
H
H
CH2CO2H
CH3


5
OH
H
CH2CO2CH2CH3
H


6
OH
H
CH2CO2H
H


7
OH
H
CH2CO2CH2CH3
CH3


8
OH
H
CH2CO2H
CH3


9
OCH3
H
CH2CO2CH2CH3
H


10
OCH3
H
CH2CO2H
H


11
OCH3
H
CH2CO2CH2CH3
CH3


12
OCH3
H
CH2CO2H
CH3


13
OCH2C6H5
H
CH2CO2CH2CH3
H


14
OCH2C6H5
H
CH2CO2H
H


15
OCH2C6H5
H
CH2CO2CH2CH3
CH3


16
OCH2C6H5
H
CH2CO2H
CH3


17
OCH2CH2C6H5
H
CH2CO2CH2CH3
H


18
OCH2CH2C6H5
H
CH2CO2H
H


19
OCH2CH2C6H5
H
CH2CO2CH2CH3
CH3


20
OCH2CH2C6H5
H
CH2CO2H
CH3


21
OCH2CH═CH2
H
CH2CO2CH2CH3
H


22
OCH2CH═CH2
H
CH2CO2H
H


23
OCH2CH═CH2
H
CH2CO2CH2CH3
CH3


24
OCH2CH═CH2
H
CH2CO2H
CH3


25
OCH2CONH2
H
CH2CO2CH2CH3
H


26
OCH2CONH2
H
CH2CO2H
H


27
OCH2CONH2
H
CH2CO2CH2CH3
CH3


28
OCH2CONH2
H
CH2CO2H
CH3


29
Cl
H
CH2CO2CH2CH3
H


30
Cl
H
CH2CO2H
H


31
Cl
H
CH2CO2CH2CH3
CH3


32
Cl
H
CH2CO2H
CH3


33
NO2
H
CH2CO2CH2CH3
H


34
NO2
H
CH2CO2H
H


35
NO2
H
CH2CO2CH2CH3
CH3


36
NO2
H
CH2CO2H
CH3


37
NH2
H
CH2CO2CH2CH3
H


38
NH2
H
CH2CO2H
H


39
NH2
H
CH2CO2CH2CH3
CH3


40
NH2
H
CH2CO2H
CH3


41
NHSO2CH3
H
CH2CO2CH2CH3
H


42
NHSO2CH3
H
CH2CO2H
H


43
NHSO2CH3
H
CH2CO2CH2CH3
CH3


44
NHSO2CH3
H
CH2CO2H
CH3


45
OH
CH2N(CH3)2
CH2CO2CH2CH3
H


46
OH
CH2N(CH3)2
CH2CO2H
H


47
OH
CH2N(CH3)2
CH2CO2CH2CH3
CH3


48
OH
CH2N(CH3)2
CH2CO2H
CH3


49
OH
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
H


50
OH
CH2N+(CH3)3Cl−
CH2CO2H
H


51
OH
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
CH3


52
OH
CH2N+(CH3)3Cl−
CH2CO2H
CH3


53
OCH3
CH2N(CH3)2
CH2CO2CH2CH3
H


54
OCH3
CH2N(CH3)2
CH2CO2H
H


55
OCH3
CH2N(CH3)2
CH2CO2CH2CH3
CH3


56
OCH3
CH2N(CH3)2
CH2CO2H
CH3


57
OCH3
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
H


58
OCH3
CH2N+(CH3)3Cl−
CH2CO2H
H


59
OCH3
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
CH3


60
OCH3
CH2N+(CH3)3Cl−
CH2CO2H
CH3


61
H
H
CH2CH2CO2CH2CH3
H


62
H
H
CH2CH2CO2H
H


63
H
H
CH2CH2CO2CH2CH3
CH3


64
H
H
CH2CH2CO2H
CH3


65
OH
H
CH2CH2CO2CH2CH3
H


66
OH
H
CH2CH2CO2H
H


67
OH
H
CH2CH2CO2CH2CH3
CH3


68
OH
H
CH2CH2CO2H
CH3


69
OCH3
H
CH2CH2CO2CH2CH3
H


70
OCH3
H
CH2CH2CO2H
H


71
OCH3
H
CH2CH2CO2CH2CH3
CH3


72
OCH3
H
CH2CH2CO2H
CH3


73
OCH2C6H5
H
CH2CH2CO2CH2CH3
H


74
OCH2C6H5
H
CH2CH2CO2H
H


75
OCH2C6H5
H
CH2CH2CO2CH2CH3
CH3


76
OCH2C6H5
H
CH2CH2CO2H
CH3


77
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
H


78
OCH2CH2C6H5
H
CH2CH2CO2H
H


79
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
CH3


80
OCH2CH2C6H5
H
CH2CH2CO2H
CH3


81
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
H


82
OCH2CH═CH2
H
CH2CH2CO2H
H


83
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
CH3


84
OCH2CH═CH2
H
CH2CH2CO2H
CH3


85
OCH2CONH2
H
CH2CH2CO2CH2CH3
H


86
OCH2CONH2
H
CH2CH2CO2H
H


87
OCH2CONH2
H
CH2CH2CO2CH2CH3
CH3


88
OCH2CONH2
H
CH2CH2CO2H
CH3


89
Cl
H
CH2CH2CO2CH2CH3
H


90
Cl
H
CH2CH2CO2H
H


91
Cl
H
CH2CH2CO2CH2CH3
CH3


92
Cl
H
CH2CH2CO2H
CH3


93
NO2
H
CH2CH2CO2CH2CH3
H


94
NO2
H
CH2CH2CO2H
H


95
NO2
H
CH2CH2CO2CH2CH3
CH3


96
NO2
H
CH2CH2CO2H
CH3


97
NH2
H
CH2CH2CO2CH2CH3
H


98
NH2
H
CH2CH2CO2H
H


99
NH2
H
CH2CH2CO2CH2CH3
CH3


100
NH2
H
CH2CH2CO2H
CH3


101
NHSO2CH3
H
CH2CH2CO2CH2CH3
H


102
NHSO2CH3
H
CH2CH2CO2H
H


103
NHSO2CH3
H
CH2CH2CO2CH2CH3
CH3


104
NHSO2CH3
H
CH2CH2CO2H
CH3


105
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3
H


106
OH
CH2N(CH3)2
CH2CH2CO2H
H


107
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3
CH3


108
OH
CH2N(CH3)2
CH2CH2CO2H
CH3


109
OH
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
H


110
OH
CH2N+(CH3)3Cl−
CH2CH2CO2H
H


111
OH
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
CH3


112
OH
CH2N+(CH3)3Cl−
CH2CH2CO2H
CH3


113
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3
H


114
OCH3
CH2N(CH3)2
CH2CH2CO2H
H


115
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3
CH3


116
OCH3
CH2N(CH3)2
CH2CH2CO2H
CH3


117
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
H


1118
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2H
H


119
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
CH3


120
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2H
CH3


121
H
H
CH2CH2PO—
H





(OCH2CH3)2



122
H
H
CH2CH2PO—(OH)2
H


123
H
H
CH2CH2PO—
CH3





(OCH2CH3)2



124
H
H
CH2CH2PO—(OH)2
CH3


125
OH
H
CH2CH2PO—
H





(OCH2CH3)2



126
OH
H
CH2CH2PO—(OH)2
H


127
OH
H
CH2CH2PO—
CH3





(OCH2CH3)2



128
OH
H
CH2CH2PO—(OH)2
CH3


129
OCH3
H
CH2CH2PO—
H





(OCH2CH3)2



130
OCH3
H
CH2CH2PO—(OH)2
H


131
OCH3
H
CH2CH2PO—
CH3





(OCH2CH3)2



132
OCH3
H
CH2CH2PO—(OH)2
CH3


133
OCH2C6H5
H
CH2CH2PO—
H





(OCH2CH3)2



134
OCH2C6H5
H
CH2CH2PO—(OH)2
H


135
OCH2C6H5
H
CH2CH2PO—
CH3





(OCH2CH3)2



136
OCH2C6H5
H
CH2CH2PO—(OH)2
CH3


137
OCH2CH2C6H5
H
CH2CH2PO—
H





(OCH2CH3)2



138
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
H


139
OCH2CH2C6H5
H
CH2CH2PO—
CH3





(OCH2CH3)2



140
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
CH3


141
OCH2CH═CH2
H
CH2CH2PO—
H





(OCH2CH3)2



142
OCH2CH═CH2
H
CH2CH2PO—(OH)2
H


143
OCH2CH═CH2
H
CH2CH2PO—
CH3





(OCH2CH3)2



144
OCH2CH═CH2
H
CH2CH2PO—(OH)2
CH3


145
OCH2CONH2
H
CH2CH2PO—
H





(OCH2CH3)2



146
OCH2CONH2
H
CH2CH2PO—(OH)2
H


147
OCH2CONH2
H
CH2CH2PO—
CH3





(OCH2CH3)2



148
OCH2CONH2
H
CH2CH2PO—(OH)2
CH3


149
Cl
H
CH2CH2PO—
H





(OCH2CH3)2



150
Cl
H
CH2CH2PO—(OH)2
H


151
Cl
H
CH2CH2PO—
CH3





(OCH2CH3)2



152
Cl
H
CH2CH2PO—(OH)2
CH3


153
NO2
H
CH2CH2PO—
H





(OCH2CH3)2



154
NO2
H
CH2CH2PO—(OH)2
H


155
NO2
H
CH2CH2PO—
CH3





(OCH2CH3)2



156
NO2
H
CH2CH2PO—(OH)2
CH3


157
NH2
H
CH2CH2PO—
H





(OCH2CH3)2



158
NH2
H
CH2CH2PO—(OH)2
H


159
NH2
H
CH2CH2PO—
CH3





(OCH2CH3)2



160
NH2
H
CH2CH2PO—(OH)2
CH3


161
NHSO2CH3
H
CH2CH2PO—
H





(OCH2CH3)2



162
NHSO2CH3
H
CH2CH2PO—(OH)2
H


163
NHSO2CH3
H
CH2CH2PO—
CH3





(OCH2CH3)2



164
NHSO2CH3
H
CH2CH2PO—(OH)2
CH3


165
OH
CH2N(CH3)2
CH2CH2PO—
H





(OCH2CH3)2



166
OH
CH2N(CH3)2
CH2CH2PO—(OH)2
H


167
OH
CH2N(CH3)2
CH2CH2PO—
CH3





(OCH2CH3)2



168
OH
CH2N(CH3)2
CH2CH2PO—(OH)2
CH3


169
OH
CH2N+(CH3)3Cl−
CH2CH2PO—
H





(OCH2CH3)2



170
OH
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
H


171
OH
CH2N+(CH3)3Cl−
CH2CH2PO—
CH3





(OCH2CH3)2



172
OH
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
CH3


173
OCH3
CH2N(CH3)2
CH2CH2PO—
H





(OCH2CH3)2



174
OCH3
CH2N(CH3)2
CH2CH2PO—(OH)2
H


175
OCH3
CH2N(CH3)2
CH2CH2PO—
CH3





(OCH2CH3)2



176
OCH3
CH2N(CH3)2
CH2CH2PO—(OH)2
CH3


177
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—
H





(OCH2CH3)2



178
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
H


179
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—
CH3





(OCH2CH3)2



180
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
CH3


181
H
H
CH2CH2CONH—
H





CH(OH)CO2H



182
H
H
CH2CH2CONH—
CH3





CH(OH)CO2H



183
OH
H
CH2CH2CONH—
H





CH(OH)CO2H



184
OH
H
CH2CH2CONH—
CH3





CH(OH)CO2H



185
OCH3
H
CH2CH2CONH—
H





CH(OH)CO2H



186
OCH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



187
OCH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



188
OCH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



189
OCH2CH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



190
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



191
OCH2CH═CH2
H
CH2CH2CONH—
H





CH(OH)CO2H



192
OCH2CH═CH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



193
OCH2CONH2
H
CH2CH2CONH—
H





CH(OH)CO2H



194
OCH2CONH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



195
Cl
H
CH2CH2CONH—
H





CH(OH)CO2H



196
Cl
H
CH2CH2CONH—
CH3





CH(OH)CO2H



197
NO2
H
CH2CH2CONH—
H





CH(OH)CO2H



198
NO2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



199
NH2
H
CH2CH2CONH—
H





CH(OH)CO2H



200
NH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



201
NHSO2CH3
H
CH2CH2CONH—
H





CH(OH)CO2H



202
NHSO2CH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



203
OH
CH2N(CH3)2
CH2CH2CONH—
H





CH(OH)CO2H



204
OH
CH2N(CH3)2
CH2CH2CONH—
CH3





CH(OH)CO2H



205
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





CH(OH)CO2H



206
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





CH(OH)CO2H



207
OCH3
CH2N(CH3)2
CH2CH2CONH—
H





CH(OH)CO2H



208
OCH3
CH2N(CH3)2
CH2CH2CONH—
CH3





CH(OH)CO2H



209
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





CH(OH)CO2H



210
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





CH(OH)CO2H



211
H
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



212
H
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



213
OH
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



214
OH
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



215
OCH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



216
OCH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



217
OCH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



218
OCH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



219
OCH2CH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



220
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



221
OCH2CH═CH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



222
OCH2CH═CH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



223
OCH2CONH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



224
OCH2CONH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



225
Cl
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



226
Cl
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



227
NO2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



228
NO2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



229
NH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



230
NH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



231
NHSO2CH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



232
NHSO2CH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



233
OH
CH2N(CH3)2
CH2CH2CONH—
H





C(CH3)2CH2SO3H



234
OH
CH2N(CH3)2
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



235
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





C(CH3)2CH2SO3H



236
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



237
OCH3
CH2N(CH3)2
CH2CH2CONH—
H





C(CH3)2CH2SO3H



238
OCH3
CH2N(CH3)2
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



239
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





C(CH3)2CH2SO3H



240
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



241
H
H
CH2-tetrazole
H


242
OH
H
CH2-tetrazole
H


243
OCH3
H
CH2-tetrazole
H


244
OCH2C6H5
H
CH2-tetrazole
H


245
Cl
H
CH2-tetrazole
H


246
CH3
H
CH2-tetrazole
H


247
H
H
CH2-tetrazole
CH3


248
OH
H
CH2-tetrazole
CH3


249
OCH3
H
CH2-tetrazole
CH3


250
OCH2C6H5
H
CH2-tetrazole
CH3


251
Cl
H
CH2-tetrazole
CH3


252
CH3
H
CH2-tetrazole
CH3
















TABLE IlIb













 











Ex. #
X
X1
Z1
R1














1
H
H
CH2CO2CH2CH3
H


2
H
H
CH2CO2H
H


3
H
H
CH2CO2CH2CH3
CH3


4
H
H
CH2CO2H
CH3


5
OH
H
CH2CO2CH2CH3
H


6
OH
H
CH2CO2H
H


7
OH
H
CH2CO2CH2CH3
CH3


8
OH
H
CH2CO2H
CH3


9
OCH3
H
CH2CO2CH2CH3
H


10
OCH3
H
CH2CO2H
H


11
OCH3
H
CH2CO2CH2CH3
CH3


12
OCH3
H
CH2CO2H
CH3


13
OCH2C6H5
H
CH2CO2CH2CH3
H


14
OCH2C6H5
H
CH2CO2H
H


15
OCH2C6H5
H
CH2CO2CH2CH3
CH3


16
OCH2C6H5
H
CH2CO2H
CH3


17
OCH2CH2C6H5
H
CH2CO2CH2CH3
H


18
OCH2CH2C6H5
H
CH2CO2H
H


19
OCH2CH2C6H5
H
CH2CO2CH2CH3
CH3


20
OCH2CH2C6H5
H
CH2CO2H
CH3


21
OCH2CH═CH2
H
CH2CO2CH2CH3
H


22
OCH2CH═CH2
H
CH2CO2H
H


23
OCH2CH═CH2
H
CH2CO2CH2CH3
CH3


24
OCH2CH═CH2
H
CH2CO2H
CH3


25
OCH2CONH2
H
CH2CO2CH2CH3
H


26
OCH2CONH2
H
CH2CO2H
H


27
OCH2CONH2
H
CH2CO2CH2CH3
CH3


28
OCH2CONH2
H
CH2CO2H
CH3


29
Cl
H
CH2CO2CH2CH3
H


30
Cl
H
CH2CO2H
H


31
Cl
H
CH2CO2CH2CH3
CH3


32
Cl
H
CH2CO2H
CH3


33
NO2
H
CH2CO2CH2CH3
H


34
NO2
H
CH2CO2H
H


35
NO2
H
CH2CO2CH2CH3
CH3


36
NO2
H
CH2CO2H
CH3


37
H
H
CH2CH2CO2CH2CH3
H


38
H
H
CH2CH2CO2H
H


39
H
H
CH2CH2CO2CH2CH3
CH3


40
H
H
CH2CH2CO2H
CH3


41
OH
H
CH2CH2CO2CH2CH3
H


42
OH
H
CH2CH2CO2H
H


43
OH
H
CH2CH2CO2CH2CH3
CH3


44
OH
H
CH2CH2CO2H
CH3


45
OCH3
H
CH2CH2CO2CH2CH3
H


46
OCH3
H
CH2CH2CO2H
H


47
OCH3
H
CH2CH2CO2CH2CH3
CH3


48
OCH3
H
CH2CH2CO2H
CH3


49
OCH2C6H5
H
CH2CH2CO2CH2CH3
H


50
OCH2C6H5
H
CH2CH2CO2H
H


51
OCH2C6H5
H
CH2CH2CO2CH2CH3
CH3


52
OCH2C6H5
H
CH2CH2CO2H
CH3


53
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
H


54
OCH2CH2C6H5
H
CH2CH2CO2H
H


55
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
CH3


56
OCH2CH2C6H5
H
CH2CH2CO2H
CH3


57
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
H


58
OCH2CH═CH2
H
CH2CH2CO2H
H


59
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
CH3


60
OCH2CH═CH2
H
CH2CH2CO2H
CH3


61
OCH2CONH2
H
CH2CH2CO2CH2CH3
H


62
OCH2CONH2
H
CH2CH2CO2H
H


63
OCH2CONH2
H
CH2CH2CO2CH2CH3
CH3


64
OCH2CONH2
H
CH2CH2CO2H
CH3


65
Cl
H
CH2CH2CO2CH2CH3
H


66
Cl
H
CH2CH2CO2H
H


67
Cl
H
CH2CH2CO2CH2CH3
CH3


68
Cl
H
CH2CH2CO2H
CH3


69
NO2
H
CH2CH2CO2CH2CH3
H


70
NO2
H
CH2CH2CO2H
H


71
NO2
H
CH2CH2CO2CH2CH3
CH3


72
NO2
H
CH2CH2CO2H
CH3


73
H
H
CH2CH2PO—(OCH2CH3)2
H


74
H
H
CH2CH2PO—(OH)2
H


75
H
H
CH2CH2PO—(OCH2CH3)2
CH3


76
H
H
CH2CH2PO—(OH)2
CH3


77
OH
H
CH2CH2PO—(OCH2CH3)2
H


78
OH
H
CH2CH2PO—(OH)2
H


79
OH
H
CH2CH2PO—(OCH2CH3)2
CH3


80
OH
H
CH2CH2PO—(OH)2
CH3


81
OCH3
H
CH2CH2PO—(OCH2CH3)2
H


82
OCH3
H
CH2CH2PO—(OH)2
H


83
OCH3
H
CH2CH2PO—(OCH2CH3)2
CH3


84
OCH3
H
CH2CH2PO—(OH)2
CH3


85
OCH2C6H5
H
CH2CH2PO—(OCH2CH3)2
H


86
OCH2C6H5
H
CH2CH2PO—(OH)2
H


87
OCH2C6H5
H
CH2CH2PO—(OCH2CH3)2
CH3


88
OCH2C6H5
H
CH2CH2PO—(OH)2
CH3


89
OCH2CH2C6H5
H
CH2CH2PO—(OCH2CH3)2
H


90
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
H


91
OCH2CH2C6H5
H
CH2CH2PO—(OCH2CH3)2
CH3


92
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
CH3


93
OCH2CH═CH2
H
CH2CH2PO—(OCH2CH3)2
H


94
OCH2CH═CH2
H
CH2CH2PO—(OH)2
H


95
OCH2CH═CH2
H
CH2CH2PO—(OCH2CH3)2
CH3


96
OCH2CH═CH2
H
CH2CH2PO—(OH)2
CH3


97
OCH2CONH2
H
CH2CH2PO—(OCH2CH3)2
H


98
OCH2CONH2
H
CH2CH2PO—(OH)2
H


99
OCH2CONH2
H
CH2CH2PO—(OCH2CH3)2
CH3


100
OCH2CONH2
H
CH2CH2PO—(OH)2
CH3


101
Cl
H
CH2CH2PO—(OCH2CH3)2
H


102
Cl
H
CH2CH2PO—(OH)2
H


103
Cl
H
CH2CH2PO—(OCH2CH3)2
CH3


104
Cl
H
CH2CH2PO—(OH)2
CH3


105
NO2
H
CH2CH2PO—(OCH2CH3)2
H


106
NO2
H
CH2CH2PO—(OH)2
H


107
NO2
H
CH2CH2PO—(OCH2CH3)2
CH3


108
NO2
H
CH2CH2PO—(OH)2
CH3


109
H
H
CH2CH2CONH—
H





CH(OH)CO2H



110
H
H
CH2CH2CONH—
CH3





CH(OH)CO2H



111
OH
H
CH2CH2CONH—
H





CH(OH)CO2H



112
OH
H
CH2CH2CONH—
CH3





CH(OH)CO2H



113
OCH3
H
CH2CH2CONH—
H





CH(OH)CO2H



114
OCH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



115
OCH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



116
OCH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



117
OCH2CH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



118
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



119
OCH2CH═CH2
H
CH2CH2CONH—
H





CH(OH)CO2H



120
OCH2CH═CH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



121
OCH2CONH2
H
CH2CH2CONH—
H





CH(OH)CO2H



122
OCH2CONH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



123
Cl
H
CH2CH2CONH—
H





CH(OH)CO2H



124
Cl
H
CH2CH2CONH—
CH3





CH(OH)CO2H



125
NO2
H
CH2CH2CONH—
H





CH(OH)CO2H



126
NO2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



127
H
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



128
H
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



129
OH
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



130
OH
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



131
OCH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



132
OCH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



133
OCH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



134
OCH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



135
OCH2CH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



136
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



137
OCH2CH═CH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



138
OCH2CH═CH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



139
OCH2CONH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



140
OCH2CONH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



141
Cl
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



142
Cl
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



143
NO2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



144
NO2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H
















TABLE IVa













 










Ex. #
X
Z
R1













1
OCH2CO2CH2CH3
H
H


2
OCH2CO2H
H
H


3
OCH2CO2CH2CH3
H
CH3


4
OCH2CO2H
H
CH3


5
OCH2CH2CO2CH2CH3
H
H


6
OCH2CH2CO2H
H
H


7
OCH2CH2CO2CH2CH3
H
CH3


8
OCH2CH2CO2H
H
CH3


9
OCH2CH2PO(OCH2CH3)2
H
H


10
OCH2CH2PO(OH)2
H
H


11
OCH2CH2PO(OCH2CH3)2
H
CH3


12
OCH2CH2PO(OH)2
H
CH3


13
OCH2CH═CHCO2CH2CH3
H
H


14
OCH2CH═CHCO2H
H
H


15
OCH2CH═CHCO2CH2CH3
H
CH3


16
OCH2CH═CHCO2H
H
CH3


17
OCH2C6H4CO2CH2CH3(2, 3 or 4)
H
H


18
OCH2C6H4CO2H(2, 3 or 4)
H
H


19
OCH2C6H4CO2CH2CH3(2, 3 or 4)
H
CH3


20
OCH2C6H4CO2H(2, 3 or 4)
H
CH3


21
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
H
H


22
OCH2C6H4CH2CO2H(2, 3 or 4)
H
H


23
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
H
CH3


24
OCH2C6H4CH2CO2H(2, 3 or 4)
H
CH3


25
OCH2CO2CH2CH3
OH
H


26
OCH2CO2H
OH
H


27
OCH2CO2CH2CH3
OH
CH3


28
OCH2CO2H
OH
CH3


29
OCH2CH2CO2CH2CH3
OH
H


30
OCH2CH2CO2H
OH
H


31
OCH2CH2CO2CH2CH3
OH
CH3


32
OCH2CH2CO2H
OH
CH3


33
OCH2CH2PO(OCH2CH3)2
OH
H


34
OCH2CH2PO(OH)2
OH
H


35
OCH2CH2PO(OCH2CH3)2
OH
CH3


36
OCH2CH2PO(OH)2
OH
CH3


37
OCH2CH═CHCO2CH2CH3
OH
H


38
OCH2CH═CHCO2H
OH
H


39
OCH2CH═CHCO2CH2CH3
OH
CH3


40
OCH2CH═CHCO2H
OH
CH3


41
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OH
H


42
OCH2C6H4CO2H(2, 3 or 4)
OH
H


43
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OH
CH3


44
OCH2C6H4CO2H(2, 3 or 4)
OH
CH3


45
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OH
H


46
OCH2C6H4CH2CO2H(2, 3 or 4)
OH
H


47
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OH
CH3


48
OCH2C6H4CH2CO2H(2, 3 or 4)
OH
CH3


49
OCH2CO2CH2CH3
OCH3
H


50
OCH2CO2H
OCH3
H


51
OCH2CO2CH2CH3
OCH3
CH3


52
OCH2CO2H
OCH3
CH3


53
OCH2CH2CO2CH2CH3
OCH3
H


54
OCH2CH2CO2H
OCH3
H


55
OCH2CH2CO2CH2CH3
OCH3
CH3


56
OCH2CH2CO2H
OCH3
CH3


57
OCH2CH2PO(OCH2CH3)2
OCH3
H


58
OCH2CH2PO(OH)2
OCH3
H


59
OCH2CH2PO(OCH2CH3)2
OCH3
CH3


60
OCH2CH2PO(OH)2
OCH3
CH3


61
OCH2CH═CHCO2CH2CH3
OCH3
H


62
OCH2CH═CHCO2H
OCH3
H


63
OCH2CH═CHCO2CH2CH3
OCH3
CH3


64
OCH2CH═CHCO2H
OCH3
CH3


65
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH3
H


66
OCH2C6H4CO2H(2, 3 or 4)
OCH3
H


67
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH3
CH3


68
OCH2C6H4CO2H(2, 3 or 4)
OCH3
CH3


69
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH3
H


70
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH3
H


71
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH3
CH3


72
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH3
CH3


73
OCH2CO2CH2CH3
OCH2CH═CH2
H


74
OCH2CO2H
OCH2CH═CH2
H


75
OCH2CO2CH2CH3
OCH2CH═CH2
CH3


76
OCH2CO2H
OCH2CH═CH2
CH3


77
OCH2CH2CO2CH2CH3
OCH2CH═CH2
H


78
OCH2CH2CO2H
OCH2CH═CH2
H


79
OCH2CH2CO2CH2CH3
OCH2CH═CH2
CH3


80
OCH2CH2CO2H
OCH2CH═CH2
CH3


81
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
H


82
OCH2CH2PO(OH)2
OCH2CH═CH2
H


83
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
CH3


84
OCH2CH2PO(OH)2
OCH2CH═CH2
CH3


85
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
H


86
OCH2CH═CHCO2H
OCH2CH═CH2
H


87
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
CH3


88
OCH2CH═CHCO2H
OCH2CH═CH2
CH3


89
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
H


90
OCH2C6H4CO2H(2, 3 or 4)
OCH2CH═CH2
H


91
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
CH3


92
OCH2C6H4CO2H(2, 3 or 4)
OCH2CH═CH2
CH3


93
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
H


94
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH2CH═CH2
H


95
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
CH3


96
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH2CH═CH2
CH3


97
OCH2CO2CH2CH3
OCH2C6CH5
H


98
OCH2CO2H
OCH2C6CH5
H


99
OCH2CO2CH2CH3
OCH2C6CH5
CH3


100
OCH2CO2H
OCH2C6CH5
CH3


101
OCH2CH2CO2CH2CH3
OCH2C6CH5
H


102
OCH2CH2CO2H
OCH2C6CH5
H


103
OCH2CH2CO2CH2CH3
OCH2C6CH5
CH3


104
OCH2CH2CO2H
OCH2C6CH5
CH3


105
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
H


106
OCH2CH2PO(OH)2
OCH2C6CH5
H


107
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
CH3


108
OCH2CH2PO(OH)2
OCH2C6CH5
CH3


109
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
H


110
OCH2CH═CHCO2H
OCH2C6CH5
H


111
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
CH3


112
OCH2CH═CHCO2H
OCH2C6CH5
CH3


113
OCH2CO2CH2CH3
OCH2CONH2
H


114
OCH2CO2H
OCH2CONH2
H


115
OCH2CO2CH2CH3
OCH2CONH2
CH3


116
OCH2CO2H
OCH2CONH2
CH3


117
OCH2CH2CO2CH2CH3
OCH2CONH2
H


118
OCH2CH2CO2H
OCH2CONH2
H


119
OCH2CH2CO2CH2CH3
OCH2CONH2
CH3


120
OCH2CH2CO2H
OCH2CONH2
CH3


121
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
H


122
OCH2CH2PO(OH)2
OCH2CONH2
H


123
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
CH3


124
OCH2CH2PO(OH)2
OCH2CONH2
CH3


125
OCH2CH═CHCO2CH2CH3
OCH2CONH2
H


126
OCH2CH═CHCO2H
OCH2CONH2
H


127
OCH2CH═CHCO2CH2CH3
OCH2CONH2
CH3


128
OCH2CH═CHCO2H
OCH2CONH2
CH3


129
OCH2-tetrazole
H
H


130
OCH2-tetrazole
H
CH3


131
OCH2-tetrazole
OH
H


132
OCH2-tetrazole
OH
CH3


133
OCH2-tetrazole
OCH3
H


134
OCH2-tetrazole
OCH3
CH3


135
OCH2-tetrazole
OCH2CH═CH2
H


136
OCH2-tetrazole
OCH2CH═CH2
CH3


137
OCH2-tetrazole
OCH2C6CH5
H


138
OCH2-tetrazole
OCH2C6CH5
CH3


139
CH2-tetrazole
H
H


140
CH2-tetrazole
H
CH3


141
CH2-tetrazole
OH
H


142
CH2-tetrazole
OH
CH3


143
CH2-tetrazole
OCH3
H


144
CH2-tetrazole
OCH3
CH3


145
CH2-tetrazole
OCH2CH═CH2
H


146
CH2-tetrazole
OCH2CH═CH2
CH3


147
CH2-tetrazole
OCH2C6CH5
H


148
CH2-tetrazole
OCH2C6CH5
CH3


149
CH2CH2-tetrazole
H
H


150
CH2CH2-tetrazole
H
CH3


151
CH2CH2-tetrazole
OH
H


152
CH2CH2-tetrazole
OH
CH3


153
CH2CH2-tetrazole
OCH3
H


154
CH2CH2-tetrazole
OCH3
CH3


155
CH2CH2-tetrazole
OCH2CH═CH2
H


156
CH2CH2-tetrazole
OCH2CH═CH2
CH3


157
CH2CH2-tetrazole
OCH2C6CH5
H


158
CH2CH2-tetrazole
OCH2C6CH5
CH3


159
OCH2CH2—N+(CH3)3X−
H
H


160
OCH2CH2—N+(CH3)3X−
H
CH3


161
OCH2CH2—N+(CH3)3X−
OCH3
H


162
OCH2CH2—N+(CH3)3X−
OCH3
CH3


163
OCH2CH2—N+(CH3)3X−
OCH2CH═CH2
H


164
OCH2CH2—N+(CH3)3X−
OCH2CH═CH2
CH3


165
OCH2CH2—N+(CH3)3X−
OCH2C6CH5
H


166
OCH2CH2—N+(CH3)3X−
OCH2C6CH5
CH3
















TABLE IVb













 










Ex. #
X1
Z
R1













1
OCH2CO2CH2CH3
H
H


2
OCH2CO2H
H
H


3
OCH2CO2CH2CH3
H
CH3


4
OCH2CO2H
H
CH3


5
OCH2CH2CO2CH2CH3
H
H


6
OCH2CH2CO2H
H
H


7
OCH2CH2CO2CH2CH3
H
CH3


8
OCH2CH2CO2H
H
CH3


9
OCH2CH2PO(OCH2CH3)2
H
H


10
OCH2CH2PO(OH)2
H
H


11
OCH2CH2PO(OCH2CH3)2
H
CH3


12
OCH2CH2PO(OH)2
H
CH3


13
OCH2CH═CHCO2CH2CH3
H
H


14
OCH2CH═CHCO2H
H
H


15
OCH2CH═CHCO2CH2CH3
H
CH3


16
OCH2CH═CHCO2H
H
CH3


17
OCH2C6H4CO2CH2CH3(2, 3 or 4)
H
H


18
OCH2C6H4CO2H(2, 3 or 4)
H
H


19
OCH2C6H4CO2CH2CH3(2, 3 or 4)
H
CH3


20
OCH2C6H4CO2H(2, 3 or 4)
H
CH3


21
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
H
H


22
OCH2C6H4CH2CO2H(2, 3 or 4)
H
H


23
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
H
CH3


24
OCH2C6H4CH2CO2H(2, 3 or 4)
H
CH3


25
OCH2CO2CH2CH3
OH
H


26
OCH2CO2H
OH
H


27
OCH2CO2CH2CH3
OH
CH3


28
OCH2CO2H
OH
CH3


29
OCH2CH2CO2CH2CH3
OH
H


30
OCH2CH2CO2H
OH
H


31
OCH2CH2CO2CH2CH3
OH
CH3


32
OCH2CH2CO2H
OH
CH3


33
OCH2CH2PO(OCH2CH3)2
OH
H


34
OCH2CH2PO(OH)2
OH
H


35
OCH2CH2PO(OCH2CH3)2
OH
CH3


36
OCH2CH2PO(OH)2
OH
CH3


37
OCH2CH═CHCO2CH2CH3
OH
H


38
OCH2CH═CHCO2H
OH
H


39
OCH2CH═CHCO2CH2CH3
OH
CH3


40
OCH2CH═CHCO2H
OH
CH3


41
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OH
H


42
OCH2C6H4CO2H(2, 3 or 4)
OH
H


43
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OH
CH3


44
OCH2C6H4CO2H(2, 3 or 4)
OH
CH3


45
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OH
H


46
OCH2C6H4CH2CO2H(2, 3 or 4)
OH
H


47
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OH
CH3


48
OCH2C6H4CH2CO2H(2, 3 or 4)
OH
CH3


49
OCH2CO2CH2CH3
OCH3
H


50
OCH2CO2H
OCH3
H


51
OCH2CO2CH2CH3
OCH3
CH3


52
OCH2CO2H
OCH3
CH3


53
OCH2CH2CO2CH2CH3
OCH3
H


54
OCH2CH2CO2H
OCH3
H


55
OCH2CH2CO2CH2CH3
OCH3
CH3


56
OCH2CH2CO2H
OCH3
CH3


57
OCH2CH2PO(OCH2CH3)2
OCH3
H


58
OCH2CH2PO(OH)2
OCH3
H


59
OCH2CH2PO(OCH2CH3)2
OCH3
CH3


60
OCH2CH2PO(OH)2
OCH3
CH3


61
OCH2CH═CHCO2CH2CH3
OCH3
H


62
OCH2CH═CHCO2H
OCH3
H


63
OCH2CH═CHCO2CH2CH3
OCH3
CH3


64
OCH2CH═CHCO2H
OCH3
CH3


65
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH3
H


66
OCH2C6H4CO2H(2, 3 or 4)
OCH3
H


67
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH3
CH3


68
OCH2C6H4CO2H(2, 3 or 4)
OCH3
CH3


69
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH3
H


70
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH3
H


71
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH3
CH3


72
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH3
CH3


73
OCH2CO2CH2CH3
OCH2CH═CH2
H


74
OCH2CO2H
OCH2CH═CH2
H


75
OCH2CO2CH2CH3
OCH2CH═CH2
CH3


76
OCH2CO2H
OCH2CH═CH2
CH3


77
OCH2CH2CO2CH2CH3
OCH2CH═CH2
H


78
OCH2CH2CO2H
OCH2CH═CH2
H


79
OCH2CH2CO2CH2CH3
OCH2CH═CH2
CH3


80
OCH2CH2CO2H
OCH2CH═CH2
CH3


81
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
H


82
OCH2CH2PO(OH)2
OCH2CH═CH2
H


83
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
CH3


84
OCH2CH2PO(OH)2
OCH2CH═CH2
CH3


85
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
H


86
OCH2CH═CHCO2H
OCH2CH═CH2
H


87
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
CH3


88
OCH2CH═CHCO2H
OCH2CH═CH2
CH3


89
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
H


90
OCH2C6H4CO2H(2, 3 or 4)
OCH2CH═CH2
H


91
OCH2C6H4CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
CH3


92
OCH2C6H4CO2H(2, 3 or 4)
OCH2CH═CH2
CH3


93
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
H


94
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH2CH═CH2
H


95
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
OCH2CH═CH2
CH3


96
OCH2C6H4CH2CO2H(2, 3 or 4)
OCH2CH═CH2
CH3


97
OCH2CO2CH2CH3
OCH2C6CH5
H


98
OCH2CO2H
OCH2C6CH5
H


99
OCH2CO2CH2CH3
OCH2C6CH5
CH3


100
OCH2CO2H
OCH2C6CH5
CH3


101
OCH2CH2CO2CH2CH3
OCH2C6CH5
H


102
OCH2CH2CO2H
OCH2C6CH5
H


103
OCH2CH2CO2CH2CH3
OCH2C6CH5
CH3


104
OCH2CH2CO2H
OCH2C6CH5
CH3


105
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
H


106
OCH2CH2PO(OH)2
OCH2C6CH5
H


107
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
CH3


108
OCH2CH2PO(OH)2
OCH2C6CH5
CH3


109
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
H


110
OCH2CH═CHCO2H
OCH2C6CH5
H


111
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
CH3


112
OCH2CH═CHCO2H
OCH2C6CH5
CH3


113
OCH2CO2CH2CH3
OCH2CONH2
H


114
OCH2CO2H
OCH2CONH2
H


115
OCH2CO2CH2CH3
OCH2CONH2
CH3


116
OCH2CO2H
OCH2CONH2
CH3


117
OCH2CH2CO2CH2CH3
OCH2CONH2
H


118
OCH2CH2CO2H
OCH2CONH2
H


119
OCH2CH2CO2CH2CH3
OCH2CONH2
CH3


120
OCH2CH2CO2H
OCH2CONH2
CH3


121
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
H


122
OCH2CH2PO(OH)2
OCH2CONH2
H


123
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
CH3


124
OCH2CH2PO(OH)2
OCH2CONH2
CH3


125
OCH2CH═CHCO2CH2CH3
OCH2CONH2
H


126
OCH2CH═CHCO2H
OCH2CONH2
H


127
OCH2CH═CHCO2CH2CH3
OCH2CONH2
CH3


128
OCH2CH═CHCO2H
OCH2CONH2
CH3


129
OCH2-tetrazole
H
H


130
OCH2-tetrazole
H
CH3


131
OCH2-tetrazole
OH
H


132
OCH2-tetrazole
OH
CH3


133
OCH2-tetrazole
OCH3
H


134
OCH2-tetrazole
OCH3
CH3


135
OCH2-tetrazole
OCH2CH═CH2
H


136
OCH2-tetrazole
OCH2CH═CH2
CH3


137
OCH2-tetrazole
OCH2C6CH5
H


138
OCH2-tetrazole
OCH2C6CH5
CH3


139
CH2-tetrazole
H
H


140
CH2-tetrazole
H
CH3


141
CH2-tetrazole
OH
H


142
CH2-tetrazole
OH
CH3


143
CH2-tetrazole
OCH3
H


144
CH2-tetrazole
OCH3
CH3


145
CH2-tetrazole
OCH2CH═CH2
H


146
CH2-tetrazole
OCH2CH═CH2
CH3


147
CH2-tetrazole
OCH2C6CH5
H


148
CH2-tetrazole
OCH2C6CH5
CH3


149
CH2CH2-tetrazole
H
H


140
CH2CH2-tetrazole
H
CH3


151
CH2CH2-tetrazole
OH
H


152
CH2CH2-tetrazole
OH
CH3


153
CH2CH2-tetrazole
OCH3
H


154
CH2CH2-tetrazole
OCH3
CH3


155
CH2CH2-tetrazole
OCH2CH═CH2
H


156
CH2CH2-tetrazole
OCH2CH═CH2
CH3


157
CH2CH2-tetrazole
OCH2C6CH5
H


158
CH2CH2-tetrazole
OCH2C6CH5
CH3


159
OCH2CH2—N+(CH3)3X−
H
H


160
OCH2CH2—N+(CH3)3X−
H
CH3


161
OCH2CH2—N+(CH3)3X−
OCH3
H


162
OCH2CH2—N+(CH3)3X−
OCH3
CH3


163
OCH2CH2—N+(CH3)3X−
OCH2CH═CH2
H


164
OCH2CH2—N+(CH3)3X−
OCH2CH═CH2
CH3


165
OCH2CH2—N+(CH3)3X−
OCH2C6CH5
H


166
OCH2CH2—N+(CH3)3X−
OCH2C6CH5
CH3
















TABLE IVc













 










Ex. #
X
Z
R1













1
OCH2CO2H
N(CH3)2
H


2
OCH2CO2CH2CH3
N(CH3)2
CH3


3
OCH2CO2H
N(CH3)2
CH3


4
OCH2CH2CO2CH2CH3
N(CH3)2
H


5
OCH2CH2CO2H
N(CH3)2
H


6
OCH2CH2CO2CH2CH3
N(CH3)2
CH3


7
OCH2CH2CO2H
N(CH3)2
CH3


8
OCH2CH2PO(OCH2CH3)2
N(CH3)2
H


9
OCH2CH2PO(OH)2
N(CH3)2
H


10
OCH2CH2PO(OCH2CH3)2
N(CH3)2
CH3


11
OCH2CH2PO(OH)2
N(CH3)2
CH3


12
OCH2CH═CHCO2CH2CH3
N(CH3)2
H


13
OCH2CH═CHCO2H
N(CH3)2
H


14
OCH2CH═CHCO2CH2CH3
N(CH3)2
CH3


15
OCH2CH═CHCO2H
N(CH3)2
CH3


16
OCH2C6H4CO2CH2CH3(2, 3 or 4)
N(CH3)2
H


17
OCH2C6H4CO2H(2, 3 or 4)
N(CH3)2
H


18
OCH2C6H4CO2CH2CH3(2, 3 or 4)
N(CH3)2
CH3


19
OCH2C6H4CO2H(2, 3 or 4)
N(CH3)2
CH3


20
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
N(CH3)2
H


21
OCH2C6H4CH2CO2H(2, 3 or 4)
N(CH3)2
H


22
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
N(CH3)2
CH3


23
OCH2C6H4CH2CO2H(2, 3 or 4)
N(CH3)2
CH3


24
OCH2CO2CH2CH3
NHCH2C6CH5
H


25
OCH2CO2H
NHCH2C6CH5
H


26
OCH2CO2CH2CH3
NHCH2C6CH5
CH3


27
OCH2CO2H
NHCH2C6CH5
CH3


28
OCH2CH2CO2CH2CH3
NHCH2C6CH5
H


29
OCH2CH2CO2H
NHCH2C6CH5
H


30
OCH2CH2CO2CH2CH3
NHCH2C6CH5
CH3


31
OCH2CH2CO2H
NHCH2C6CH5
CH3


32
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
H


33
OCH2CH2PO(OH)2
NHCH2C6CH5
H


34
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
CH3


35
OCH2CH2PO(OH)2
NHCH2C6CH5
CH3


36
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
H


37
OCH2CH═CHCO2H
NHCH2C6CH5
H


38
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
CH3


39
OCH2CH═CHCO2H
NHCH2C6CH5
CH3


40
OCH2CO2CH2CH3
NHCH2CONH2
H


41
OCH2CO2H
NHCH2CONH2
H


42
OCH2CO2CH2CH3
NHCH2CONH2
CH3


43
OCH2CO2H
NHCH2CONH2
CH3


44
OCH2CH2CO2CH2CH3
NHCH2CONH2
H


45
OCH2CH2CO2H
NHCH2CONH2
H


46
OCH2CH2CO2CH2CH3
NHCH2CONH2
CH3


47
OCH2CH2CO2H
NHCH2CONH2
CH3


48
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
H


49
OCH2CH2PO(OH)2
NHCH2CONH2
H


50
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
CH3


51
OCH2CH2PO(OH)2
NHCH2CONH2
CH3


52
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
H


53
OCH2CH═CHCO2H
NHCH2CONH2
H


54
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
CH3


55
OCH2CH═CHCO2H
NHCH2CONH2
CH3


56
OCH2C6H4CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
H


57
OCH2C6H4CO2H(2, 3 or 4)
NHCH2CONH2
H


58
OCH2C6H4CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
CH3


59
OCH2C6H4CO2H(2, 3 or 4)
NHCH2CONH2
CH3


60
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
H


61
OCH2C6H4CH2CO2H(2, 3 or 4)
NHCH2CONH2
H


62
OCH2C6H4CH2CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
CH3


63
OCH2C6H4CH2CO2H(2, 3 or 4)
NHCH2CONH2
CH3


64
OCH2-tetrazole
N(CH3)2
H


65
OCH2-tetrazole
N(CH3)2
CH3


66
OCH2-tetrazole
NHCH2C6CH5
H


67
OCH2-tetrazole
NHCH2C6CH5
CH3


68
CH2-tetrazole
N(CH3)2
H


69
CH2-tetrazole
N(CH3)2
CH3


70
CH2-tetrazole
NHCH2C6CH5
H


71
CH2-tetrazole
NHCH2C6CH5
CH3
















TABLE IVd













 










Ex. #
X1
Z
R1













1
OCH2CO2H
N(CH3)2
H


2
OCH2CO2CH2CH3
N(CH3)2
CH3


3
OCH2CO2H
N(CH3)2
CH3


4
OCH2CH2CO2CH2CH3
N(CH3)2
H


5
OCH2CH2CO2H
N(CH3)2
H


6
OCH2CH2CO2CH2CH3
N(CH3)2
CH3


7
OCH2CH2CO2H
N(CH3)2
CH3


8
OCH2CH2PO(OCH2CH3)2
N(CH3)2
H


9
OCH2CH2PO(OH)2
N(CH3)2
H


10
OCH2CH2PO(OCH2CH3)2
N(CH3)2
CH3


11
OCH2CH2PO(OH)2
N(CH3)2
CH3


12
OCH2CH═CHCO2CH2CH3
N(CH3)2
H


13
OCH2CH═CHCO2H
N(CH3)2
H


14
OCH2CH═CHCO2CH2CH3
N(CH3)2
CH3


15
OCH2CH═CHCO2H
N(CH3)2
CH3


16
OCH2C6H4CO2CH2CH3(2, 3 or 4)
N(CH3)2
H


17
OCH2C6H4CO2H(2, 3 or 4)
N(CH3)2
H


18
OCH2C6H4CO2CH2CH3(2, 3 or 4)
N(CH3)2
CH3


19
OCH2C6H4CO2H(2, 3 or 4)
N(CH3)2
CH3


20
OCH2C6H4CH2CO2CH2CH3(2, 3
N(CH3)2
H



or 4)




21
OCH2C6H4CH2CO2H(2, 3 or 4)
N CH3
2 H


22
OCH2C6H4CH2CO2CH2CH3(2, 3
N(CH3)2
CH3



or 4)




23
OCH2C6H4CH2CO2H(2, 3 or 4)
N(CH3)2
CH3


24
OCH2CO2CH2CH3
NHCH2C6CH5
H


25
OCH2CO2H
NHCH2C6CH5
H


26
OCH2CO2CH2CH3
NHCH2C6CH5
CH3


27
OCH2CO2H
NHCH2C6CH5
CH3


28
OCH2CH2CO2CH2CH3
NHCH2C6CH5
H


29
OCH2CH2CO2H
NHCH2C6CH5
H


30
OCH2CH2CO2CH2CH3
NHCH2C6CH5
CH3


31
OCH2CH2CO2H
NHCH2C6CH5
CH3


32
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
H


33
OCH2CH2PO(OH)2
NHCH2C6CH5
H


34
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
CH3


35
OCH2CH2PO(OH)2
NHCH2C6CH5
CH3


36
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
H


37
OCH2CH═CHCO2H
NHCH2C6CH5
H


38
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
CH3


39
OCH2CH═CHCO2H
NHCH2C6CH5
CH3


40
OCH2CO2CH2CH3
NHCH2CONH2
H


41
OCH2CO2H
NHCH2CONH2
H


42
OCH2CO2CH2CH3
NHCH2CONH2
CH3


43
OCH2CO2H
NHCH2CONH2
CH3


44
OCH2CH2CO2CH2CH3
NHCH2CONH2
H


45
OCH2CH2CO2H
NHCH2CONH2
H


46
OCH2CH2CO2CH2CH3
NHCH2CONH2
CH3


47
OCH2CH2CO2H
NHCH2CONH2
CH3


48
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
H


49
OCH2CH2PO(OH)2
NHCH2CONH2
H


50
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
CH3


51
OCH2CH2PO(OH)2
NHCH2CONH2
CH3


52
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
H


53
OCH2CH═CHCO2H
NHCH2CONH2
H


54
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
CH3


55
OCH2CH═CHCO2H
NHCH2CONH2
CH3


56
OCH2C6H4CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
H


57
OCH2C6H4CO2H(2, 3 or 4)
NHCH2CONH2
H


58
OCH2C6H4CO2CH2CH3(2, 3 or 4)
NHCH2CONH2
CH3


59
OCH2C6H4CO2H(2, 3 or 4)
NHCH2CONH2
CH3


60
OCH2C6H4CH2CO2CH2CH3(2, 3
NHCH2CONH2
H



or 4)




61
OCH2C6H4CH2CO2H(2, 3 or 4)
NHCH2CONH2
H


62
OCH2C6H4CH2CO2CH2CH3(2, 3
NHCH2CONH2
CH3



or 4)




63
OCH2C6H4CH2CO2H(2, 3 or 4)
NHCH2CONH2
CH3


64
OCH2-tetrazole
N(CH3)2
H


65
OCH2-tetrazole
N(CH3)2
CH3


66
OCH2-tetrazole
NHCH2C6CH5
H


67
OCH2-tetrazole
NHCH2C6CH5
CH3


68
CH2-tetrazole
N(CH3)2
H


69
CH2-tetrazole
N(CH3)2
CH3


70
CH2-tetrazole
NHCH2C6CH5
H


71
CH2-tetrazole
NHCH2C6CH5
CH3
















TABLE V













 











Ex. #
X
X1
Z
R1














1.
H
H
OH
CO2CH2CH3


2.
H
H
OH
CO2H


3.
H
H
OH
CH2CO2CH2CH3


4.
H
H
OH
CH2CO2H


5.
H
H
OH
CH2CH2CO2CH2CH3


6.
H
H
OH
CH2CH2CO2H


7.
H
H
OH
CH2CH═CHCO2H


8.
H
H
OH
CH2CH═CHCO2H


9.
H
H
OH
CH2CH2P—






O(OCH2CH3)2


10.
H
H
OH
CH2CH2P—O(OH)2


11.
OH
H
OH
CO2CH2CH3


12.
OH
H
OH
CO2H


13.
OH
H
OH
CH2CO2CH2CH3


14.
OH
H
OH
CH2CO2H


15.
OH
H
OH
CH2CH2CO2CH2CH3


16.
OH
H
OH
CH2CH2CO2H


17.
OH
H
OH
CH2CH═CHCO2H


18.
OH
H
OH
CH2CH═CHCO2H


19.
OH
H
OH
CH2CH2P—






O(OCH2CH3)2


20.
OH
H
OH
CH2CH2P—O(OH)2


21.
OCH3
H
OH
CO2CH2CH3


22.
OCH3
H
OH
CO2H


23.
OCH3
H
OH
CH2CO2CH2CH3


24.
OCH3
H
OH
CH2CO2H


25.
OCH3
H
OH
CH2CH2CO2CH2CH3


26.
OCH3
H
OH
CH2CH2CO2H


27.
OCH3
H
OH
CH2CH═CHCO2H


28.
OCH3
H
OH
CH2CH═CHCO2H


29.
OCH3
H
OH
CH2CH2P—






O(OCH2CH3)2


30.
OCH3
H
OH
CH2CH2P—O(OH)2


31.
OCH2CH═CH2
H
OH
CO2CH2CH3


32.
OCH2CH═CH2
H
OH
CO2H


33.
OCH2CH═CH2
H
OH
CH2CO2CH2CH3


34.
OCH2CH═CH2
H
OH
CH2CO2H


35.
OCH2CH═CH2
H
OH
CH2CH2CO2CH2CH3


36.
OCH2CH═CH2
H
OH
CH2CH2CO2H


37.
OCH2CH═CH2
H
OH
CH2CH═CHCO2H


38.
OCH2CH═CH2
H
OH
CH2CH═CHCO2H


39.
OCH2CH═CH2
H
OH
CH2CH2P—






O(OCH2CH3)2


40.
OCH2CH═CH2
H
OH
CH2CH2P—O(OH)2


41.
OCH2C6H5
H
OH
CO2CH2CH3


42.
OCH2C6H5
H
OH
CO2H


43.
OCH2C6H5
H
OH
CH2CO2CH2CH3


44.
OCH2C6H5
H
OH
CH2CO2H


45.
OCH2C6H5
H
OH
CH2CH2CO2CH2CH3


46.
OCH2C6H5
H
OH
CH2CH2CO2H


47.
OCH2C6H5
H
OH
CH2CH═CHCO2H


48.
OCH2C6H5
H
OH
CH2CH═CHCO2H


49.
OCH2C6H5
H
OH
CH2CH2P—






O(OCH2CH3)2


50.
OCH2C6H5
H
OH
CH2CH2P—O(OH)2


51.
Cll
H
OH
CO2CH2CH3


52.
Cl
H
OH
CO2H


53.
Cl
H
OH
CH2CO2CH2CH3


54.
Cl
H
OH
CH2CO2H


55.
Cl
H
OH
CH2CH2CO2CH2CH3


56.
Cl
H
OH
CH2CH2CO2H


57.
Cl
H
OH
CH2CH═CHCO2H


58.
Cl
H
OH
CH2CH═CHCO2H


59.
Cl
H
OH
CH2CH2P—






O(OCH2CH3)2


60.
Cl
H
OH
CH2CH2P—O(OH)2


61.
NO2
H
OH
CO2CH2CH3


62.
NO2
H
OH
CO2H


63.
NO2
H
OH
CH2CO2CH2CH3


64.
NO2
H
OH
CH2CO2H


65.
NO2
H
OH
CH2CH2CO2CH2CH3


66.
NO2
H
OH
CH2CH2CO2H


67.
NO2
H
OH
CH2CH═CHCO2H


68.
NO2
H
OH
CH2CH═CHCO2H


69.
NO2
H
OH
CH2CH2P—






O(OCH2CH3)2


70.
NO2
H
OH
CH2CH2P—O(OH)2


71.
NH2
H
OH
CO2CH2CH3


72.
NH2
H
OH
CO2H


73.
NH2
H
OH
CH2CO2CH2CH3


74.
NH2
H
OH
CH2CO2H


75.
NH2
H
OH
CH2CH2CO2CH2CH3


76.
NH2
H
OH
CH2CH2CO2H


77.
NH2
H
OH
CH2CH═CHCO2H


78.
NH2
H
OH
CH2CH═CHCO2H


79.
NH2
H
OH
CH2CH2P—






O(OCH2CH3)2


80.
NH2
H
OH
CH2CH2P—O(OH)2


81.
NHSO2CH3
H
OH
H


82.
NHSO2CH3
H
OH
CH3


83.
NHSO2CH3
H
OH
CO2CH2CH3


84.
NHSO2CH3
H
OH
CO2H


85.
NHSO2CH3
H
OH
CH2CO2CH2CH3


86.
NHSO2CH3
H
OH
CH2CO2H


87.
NHSO2CH3
H
OH
CH2CH2CO2CH2CH3


88.
NHSO2CH3
H
OH
CH2CH2CO2H


89.
NHSO2CH3
H
OH
CH2CH═CHCO2H


90.
NHSO2CH3
H
OH
CH2CH═CHCO2H


91.
NHSO2CH3
H
OH
CH2CH2P—






O(OCH2CH3)2


92.
NHSO2CH3
H
OH
CH2CH2P—O(OH)2


93.
OCH2CONH2
H
OH
H


94.
OCH2CONH2
H
OH
CH3


95.
OCH2CONH2
H
OH
CO2CH2CH3


96.
OCH2CONH2
H
OH
CO2H


97.
OCH2CONH2
H
OH
CH2CO2CH2CH3


98.
OCH2CONH2
H
OH
CH2CO2H


99.
OCH2CONH2
H
OH
CH2CH2CO2CH2CH3


100.
OCH2CONH2
H
OH
CH2CH2CO2H


101.
OCH2CONH2
H
OH
CH2CH═CHCO2H


102.
OCH2CONH2
H
OH
CH2CH═CHCO2H


103.
OCH2CONH2
H
OH
CH2CH2P—






O(OCH2CH3)2


104.
OCH2CONH2
H
OH
CH2CH2P—O(OH)2


105.
OH
CH2N(CH3)2
OH
CO2CH2CH3


106.
OH
CH2N(CH3)2
OH
CO2H


107.
OH
CH2N(CH3)2
OH
CH2CO2CH2CH3


108.
OH
CH2N(CH3)2
OH
CH2CO2H


109.
OH
CH2N(CH3)2
OH
CH2CH2CO2CH2CH3


110.
OH
CH2N(CH3)2
OH
CH2CH2CO2H


111.
OH
CH2N(CH3)2
OH
CH2CH═CHCO2H


112.
OH
CH2N(CH3)2
OH
CH2CH═CHCO2H


113.
OH
CH2N(CH3)2
OH
CH2CH2P—






O(OCH2CH3)2


114.
OH
CH2N(CH3)2
OH
CH2CH2P—O(OH)2


115.
OCH3
CH2N(CH3)2
OH
CO2CH2CH3


116.
OCH3
CH2N(CH3)2
OH
CO2H


117.
OCH3
CH2N(CH3)2
OH
CH2CO2CH2CH3


118.
OCH3
CH2N(CH3)2
OH
CH2CO2H


119.
OCH3
CH2N(CH3)2
OH
CH2CH2CO2CH2CH3


120.
OCH3
CH2N(CH3)2
OH
CH2CH2CO2H


121.
OCH3
CH2N(CH3)2
OH
CH2CH═CHCO2H


122.
OCH3
CH2N(CH3)2
OH
CH2CH═CHCO2H


123.
OCH3
CH2N(CH3)2
OH
CH2CH2P—






O(OCH2CH3)2


124.
OCH3
CH2N(CH3)2
OH
CH2CH2P—O(OH)2


125.
OH
CH2N+(CH3)3
OH
H




Cl−




126.
OH
CH2N+(CH3)3
OH
CH3




Cl−




127.
OH
CH2N+(CH3)3
OH
CO2CH2CH3




Cl−




128.
OH
CH2N+(CH3)3
OH
CO2H




Cl−




129.
OH
CH2N+(CH3)3
OH
CH2CO2CH2CH3




Cl−




130.
OH
CH2N+(CH3)3
OH
CH2CO2H




Cl−




131.
OH
CH2N+(CH3)3
OH
CH2CH2CO2CH2CH3




Cl−




132.
OH
CH2N+(CH3)3
OH
CH2CH2CO2H




Cl−




133.
OH
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




134.
OH
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




135.
OH
CH2N+(CH3)3
OH
CH2CH2P—




Cl−

O(OCH2CH3)2


136.
OH
CH2N+(CH3)3
OH
CH2CH2P—O(OH)2




Cl−




137.
OCH3
CH2N+(CH3)3
OH
H




Cl−




138.
OCH3
CH2N+(CH3)3
OH
CH3




Cl−




139.
OCH3
CH2N+(CH3)3
OH
CO2CH2CH3




Cl−




140.
OCH3
CH2N+(CH3)3
OH
CO2H




Cl−




141.
OCH3
CH2N+(CH3)3
OH
CH2CO2CH2CH3




Cl−




142.
OCH3
CH2N+(CH3)3
OH
CH2CO2H




Cl−




143.
OCH3
CH2N+(CH3)3
OH
CH2CH2CO2CH2CH3




Cl−




144.
OCH3
CH2N+(CH3)3
OH
CH2CH2CO2H




Cl−




145.
OCH3
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




146.
OCH3
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




147.
OCH3
CH2N+(CH3)3
OH
CH2CH2P—




Cl−

O(OCH2CH3)2


148.
OCH3
CH2N+(CH3)3
OH
CH2CH2P—O(OH)2




Cl−




149.
H
H
OCH3
CO2CH2CH3


150.
H
H
OCH3
CO2H


151.
H
H
OCH3
CH2CO2CH2CH3


152.
H
H
OCH3
CH2CO2H


153.
H
H
OCH3
CH2CH2CO2CH2CH3


154.
H
H
OCH3
CH2CH2CO2H


155.
H
H
OCH3
CH2CH═CHCO2H


156.
H
H
OCH3
CH2CH═CHCO2H


157.
H
H
OCH3
CH2CH2P—






O(OCH2CH3)2


158.
H
H
OCH3
CH2CH2P—O(OH)2


159.
OH
H
OCH3
CO2CH2CH3


160.
OH
H
OCH3
CO2H


161.
OH
H
OCH3
CH2CO2CH2CH3


162.
OH
H
OCH3
CH2CO2H


163.
OH
H
OCH3
CH2CH2CO2CH2CH3


164.
OH
H
OCH3
CH2CH2CO2H


165.
OH
H
OCH3
CH2CH═CHCO2H


166.
OH
H
OCH3
CH2CH═CHCO2H


167.
OH
H
OCH3
CH2CH2P—






O(OCH2CH3)2


168.
OH
H
OCH3
CH2CH2P—O(OH)2


169.
OCH3
H
OCH3
CO2CH2CH3


170.
OCH3
H
OCH3
CO2H


171.
OCH3
H
OCH3
CH2CO2CH2CH3


172.
OCH3
H
OCH3
CH2CO2H


173.
OCH3
H
OCH3
CH2CH2CO2CH2CH3


174.
OCH3
H
OCH3
CH2CH2CO2H


175.
OCH3
H
OCH3
CH2CH═CHCO2H


176.
OCH3
H
OCH3
CH2CH═CHCO2H


177.
OCH3
H
OCH3
CH2CH2P—






O(OCH2CH3)2


178.
OCH3
H
OCH3
CH2CH2P—O(OH)2


179.
OCH2CH═CH2
H
OCH3
CO2CH2CH3


180.
OCH2CH═CH2
H
OCH3
CO2H


181.
OCH2CH═CH2
H
OCH3
CH2CO2CH2CH3


182.
OCH2CH═CH2
H
OCH3
CH2CO2H


183.
OCH2CH═CH2
H
OCH3
CH2CH2CO2CH2CH3


184.
OCH2CH═CH2
H
OCH3
CH2CH2CO2H


185.
OCH2CH═CH2
H
OCH3
CH2CH═CHCO2H


186.
OCH2CH═CH2
H
OCH3
CH2CH═CHCO2H


187.
OCH2CH═CH2
H
OCH3
CH2CH2P—






O(OCH2CH3)2


188.
OCH2CH═CH2
H
OCH3
CH2CH2P—O(OH)2


189.
OCH2C6H5
H
OCH3
CO2CH2CH3


190.
OCH2C6H5
H
OCH3
CO2H


191.
OCH2C6H5
H
OCH3
CH2CO2CH2CH3


192.
OCH2C6H5
H
OCH3
CH2CO2H


193.
OCH2C6H5
H
OCH3
CH2CH2CO2CH2CH3


194.
OCH2C6H5
H
OCH3
CH2CH2CO2H


195.
OCH2C6H5
H
OCH3
CH2CH═CHCO2H


196.
OCH2C6H5
H
OCH3
CH2CH═CHCO2H


197.
OCH2C6H5
H
OCH3
CH2CH2P—






O(OCH2CH3)2


198.
OCH2C6H5
H
OCH3
CH2CH2P—O(OH)2


199.
Cl
H
OCH3
CO2CH2CH3


200.
Cl
H
OCH3
CO2H


201.
Cl
H
OCH3
CH2CO2CH2CH3


202.
Cl
H
OCH3
CH2CO2H


203.
Cl
H
OCH3
CH2CH2CO2CH2CH3


204.
Cl
H
OCH3
CH2CH2CO2H


205.
Cl
H
OCH3
CH2CH═CHCO2H


206.
Cl
H
OCH3
CH2CH═CHCO2H


207.
Cl
H
OCH3
CH2CH2P—






O(OCH2CH3)2


208.
Cl
H
OCH3
CH2CH2P—O(OH)2


209.
NO2
H
OCH3
CO2CH2CH3


210.
NO2
H
OCH3
CO2H


211.
NO2
H
OCH3
CH2CO2CH2CH3


212.
NO2
H
OCH3
CH2CO2H


213.
NO2
H
OCH3
CH2CH2CO2CH2CH3


214.
NO2
H
OCH3
CH2CH2CO2H


215.
NO2
H
OCH3
CH2CH═CHCO2H


216.
NO2
H
OCH3
CH2CH═CHCO2H


217.
NO2
H
OCH3
CH2CH2P—






O(OCH2CH3)2


218.
NO2
H
OCH3
CH2CH2P—O(OH)2


219.
NH2
H
OCH3
CO2CH2CH3


220.
NH2
H
OCH3
CO2H


221.
NH2
H
OCH3
CH2CO2CH2CH3


222.
NH2
H
OCH3
CH2CO2H


223.
NH2
H
OCH3
CH2CH2CO2CH2CH3


224.
NH2
H
OCH3
CH2CH2CO2H


225.
NH2
H
OCH3
CH2CH═CHCO2H


226.
NH2
H
OCH3
CH2CH═CHCO2H


227.
NH2
H
OCH3
CH2CH2P—






O(OCH2CH3)2


228.
NH2
H
OCH3
CH2CH2P—O(OH)2


229.
NHSO2CH3
H
OCH3
H


230.
NHSO2CH3
H
OCH3
CH3


231.
NHSO2CH3
H
OCH3
CO2CH2CH3


232.
NHSO2CH3
H
OCH3
CO2H


233.
NHSO2CH3
H
OCH3
CH2CO2CH2CH3


234.
NHSO2CH3
H
OCH3
CH2CO2H


235.
NHSO2CH3
H
OCH3
CH2CH2CO2CH2CH3


236.
NHSO2CH3
H
OCH3
CH2CH2CO2H


237.
NHSO2CH3
H
OCH3
CH2CH═CHCO2H


238.
NHSO2CH3
H
OCH3
CH2CH═CHCO2H


239.
NHSO2CH3
H
OCH3
CH2CH2P—






O(OCH2CH3)2


240.
NHSO2CH3
H
OCH3
CH2CH2P—O(OH)2


241.
OCH2CONH2
H
OCH3
H


242.
OCH2CONH2
H
OCH3
CH3


243.
OCH2CONH2
H
OCH3
CO2CH2CH3


244.
OCH2CONH2
H
OCH3
CO2H


245.
OCH2CONH2
H
OCH3
CH2CO2CH2CH3


246.
OCH2CONH2
H
OCH3
CH2CO2H


247.
OCH2CONH2
H
OCH3
CH2CH2CO2CH2CH3


248.
OCH2CONH2
H
OCH3
CH2CH2CO2H


249.
OCH2CONH2
H
OCH3
CH2CH═CHCO2H


250.
OCH2CONH2
H
OCH3
CH2CH═CHCO2H


251.
OCH2CONH2
H
OCH3
CH2CH2P—






O(OCH2CH3)2


252.
OCH2CONH2
H
OCH3
CH2CH2P—O(OH)2


253.
OH
CH2N(CH3)2
OCH3
CO2CH2CH3


254.
OH
CH2N(CH3)2
OCH3
CO2H


255.
OH
CH2N(CH3)2
OCH3
CH2CO2CH2CH3


256.
OH
CH2N(CH3)2
OCH3
CH2CO2H


257.
OH
CH2N(CH3)2
OCH3
CH2CH2CO2CH2CH3


258.
OH
CH2N(CH3)2
OCH3
CH2CH2CO2H


259.
OH
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


260.
OH
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


261.
OH
CH2N(CH3)2
OCH3
CH2CH2P—






O(OCH2CH3)2


262.
OH
CH2N(CH3)2
OCH3
CH2CH2P—O(OH)2


263.
OCH3
CH2N(CH3)2
OCH3
CO2CH2CH3


264.
OCH3
CH2N(CH3)2
OCH3
CO2H


265.
OCH3
CH2N(CH3)2
OCH3
CH2CO2CH2CH3


266.
OCH3
CH2N(CH3)2
OCH3
CH2CO2H


267.
OCH3
CH2N(CH3)2
OCH3
CH2CH2CO2CH2CH3


268.
OCH3
CH2N(CH3)2
OCH3
CH2CH2CO2H


269.
OCH3
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


270.
OCH3
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


271.
OCH3
CH2N(CH3)2
OCH3
CH2CH2P—






O(OCH2CH3)2


272.
OCH3
CH2N(CH3)2
OCH3
CH2CH2P—O(OH)2


273.
OH
CH2N+(CH3)3
OCH3
H




Cl−




274.
OH
CH2N+(CH3)3
OCH3
CH3




Cl−




275.
OH
CH2N+(CH3)3
OCH3
CO2CH2CH3




Cl−




276.
OH
CH2N+(CH3)3
OCH3
CO2H




Cl−




277.
OH
CH2N+(CH3)3
OCH3
CH2CO2CH2CH3




Cl−




278.
OH
CH2N+(CH3)3
OCH3
CH2CO2H




Cl−




279.
OH
CH2N+(CH3)3
OCH3
CH2CH2CO2CH2CH3




Cl−




280.
OH
CH2N+(CH3)3
OCH3
CH2CH2CO2H




Cl−




281.
OH
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




282.
OH
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




283.
OH
CH2N+(CH3)3
OCH3
CH2CH2P—




Cl−

O(OCH2CH3)2


284.
OH
CH2N+(CH3)3
OCH3
CH2CH2P—O(OH)2




Cl−




285.
OCH3
CH2N+(CH3)3
OCH3
H




Cl−




286.
OCH3
CH2N+(CH3)3
OCH3
CH3




Cl−




287.
OCH3
CH2N+(CH3)3
OCH3
CO2CH2CH3




Cl−




288.
OCH3
CH2N+(CH3)3
OCH3
CO2H




Cl−




289.
OCH3
CH2N+(CH3)3
OCH3
CH2CO2CH2CH3




Cl−




290.
OCH3
CH2N+(CH3)3
OCH3
CH2CO2H




Cl−




291.
OCH3
CH2N+(CH3)3
OCH3
CH2CH2CO2CH2CH3




Cl−




292.
OCH3
CH2N+(CH3)3
OCH3
CH2CH2CO2H




Cl−




293.
OCH3
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




294.
OCH3
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




295.
OCH3
CH2N+(CH3)3
OCH3
CH2CH2P—




Cl−

O(OCH2CH3)2


296.
OCH3
CH2N+(CH3)3
OCH3
CH2CH2P—O(OH)2




Cl−




297.
H
H
OCH2C6H5
CO2CH2CH3


298.
H
H
OCH2C6H5
CO2H


299.
H
H
OCH2C6H5
CH2CO2CH2CH3


300.
H
H
OCH2C6H5
CH2CO2H


301.
H
H
OCH2C6H5
CH2CH2CO2CH2CH3


302.
H
H
OCH2C6H5
CH2CH2CO2H


303.
H
H
OCH2C6H5
CH2CH═CHCO2H


304.
H
H
OCH2C6H5
CH2CH═CHCO2H


305.
H
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


306.
H
H
OCH2C6H5
CH2CH2P—O(OH)2


307.
OH
H
OCH2C6H5
CO2CH2CH3


308.
OH
H
OCH2C6H5
CO2H


309.
OH
H
OCH2C6H5
CH2CO2CH2CH3


310.
OH
H
OCH2C6H5
CH2CO2H


311.
OH
H
OCH2C6H5
CH2CH2CO2CH2CH3


312.
OH
H
OCH2C6H5
CH2CH2CO2H


313.
OH
H
OCH2C6H5
CH2CH═CHCO2H


314.
OH
H
OCH2C6H5
CH2CH═CHCO2H


315.
OH
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


316.
OH
H
OCH2C6H5
CH2CH2P—O(OH)2


317.
OCH3
H
OCH2C6H5
CO2CH2CH3


318.
OCH3
H
OCH2C6H5
CO2H


319.
OCH3
H
OCH2C6H5
CH2CO2CH2CH3


320.
OCH3
H
OCH2C6H5
CH2CO2H


321.
OCH3
H
OCH2C6H5
CH2CH2CO2CH2CH3


322.
OCH3
H
OCH2C6H5
CH2CH2CO2H


323.
OCH3
H
OCH2C6H5
CH2CH═CHCO2H


324.
OCH3
H
OCH2C6H5
CH2CH═CHCO2H


325.
OCH3
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


326.
OCH3
H
OCH2C6H5
CH2CH2P—O(OH)2


327.
OCH2CH═CH2
H
OCH2C6H5
CO2CH2CH3


328.
OCH2CH═CH2
H
OCH2C6H5
CO2H


329.
OCH2CH═CH2
H
OCH2C6H5
CH2CO2CH2CH3


330.
OCH2CH═CH2
H
OCH2C6H5
CH2CO2H


331.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2CO2CH2CH3


332.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2CO2H


333.
OCH2CH═CH2
H
OCH2C6H5
CH2CH═CHCO2H


334.
OCH2CH═CH2
H
OCH2C6H5
CH2CH═CHCO2H


335.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


336.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2P—O(OH)2


337.
OCH2C6H5
H
OCH2C6H5
CO2CH2CH3


338.
OCH2C6H5
H
OCH2C6H5
CO2H


339.
OCH2C6H5
H
OCH2C6H5
CH2CO2CH2CH3


340.
OCH2C6H5
H
OCH2C6H5
CH2CO2H


341.
OCH2C6H5
H
OCH2C6H5
CH2CH2CO2CH2CH3


342.
OCH2C6H5
H
OCH2C6H5
CH2CH2CO2H


343.
OCH2C6H5
H
OCH2C6H5
CH2CH═CHCO2H


344.
OCH2C6H5
H
OCH2C6H5
CH2CH═CHCO2H


345.
OCH2C6H5
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


346.
OCH2C6H5
H
OCH2C6H5
CH2CH2P—O(OH)2


347.
Cl
H
OCH2C6H5
CO2CH2CH3


348.
Cl
H
OCH2C6H5
CO2H


349.
Cl
H
OCH2C6H5
CH2CO2CH2CH3


350.
Cl
H
OCH2C6H5
CH2CO2H


351.
Cl
H
OCH2C6H5
CH2CH2CO2CH2CH3


352.
Cl
H
OCH2C6H5
CH2CH2CO2H


353.
Cl
H
OCH2C6H5
CH2CH═CHCO2H


354.
Cl
H
OCH2C6H5
CH2CH═CHCO2H


355.
Cl
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


356.
Cl
H
OCH2C6H5
CH2CH2P—O(OH)2


357.
NO2
H
OCH2C6H5
CO2CH2CH3


358.
NO2
H
OCH2C6H5
CO2H


359.
NO2
H
OCH2C6H5
CH2CO2CH2CH3


360.
NO2
H
OCH2C6H5
CH2CO2H


361.
NO2
H
OCH2C6H5
CH2CH2CO2CH2CH3


362.
NO2
H
OCH2C6H5
CH2CH2CO2H


363.
NO2
H
OCH2C6H5
CH2CH═CHCO2H


364.
NO2
H
OCH2C6H5
CH2CH═CHCO2H


365.
NO2
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


366.
NO2
H
OCH2C6H5
CH2CH2P—O(OH)2


367.
NH2
H
OCH2C6H5
CO2CH2CH3


368.
NH2
H
OCH2C6H5
CO2H


369.
NH2
H
OCH2C6H5
CH2CO2CH2CH3


370.
NH2
H
OCH2C6H5
CH2CO2H


371.
NH2
H
OCH2C6H5
CH2CH2CO2CH2CH3


372.
NH2
H
OCH2C6H5
CH2CH2CO2H


373.
NH2
H
OCH2C6H5
CH2CH═CHCO2H


374.
NH2
H
OCH2C6H5
CH2CH═CHCO2H


375.
NH2
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


376.
NH2
H
OCH2C6H5
CH2CH2P—O(OH)2


377.
NHSO2CH3
H
OCH2C6H5
H


378.
NHSO2CH3
H
OCH2C6H5
CH3


379.
NHSO2CH3
H
OCH2C6H5
CO2CH2CH3


380.
NHSO2CH3
H
OCH2C6H5
CO2H


381.
NHSO2CH3
H
OCH2C6H5
CH2CO2CH2CH3


382.
NHSO2CH3
H
OCH2C6H5
CH2CO2H


383.
NHSO2CH3
H
OCH2C6H5
CH2CH2CO2CH2CH3


384.
NHSO2CH3
H
OCH2C6H5
CH2CH2CO2H


385.
NHSO2CH3
H
OCH2C6H5
CH2CH═CHCO2H


386.
NHSO2CH3
H
OCH2C6H5
CH2CH═CHCO2H


387.
NHSO2CH3
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


388.
NHSO2CH3
H
OCH2C6H5
CH2CH2P—O(OH)2


389.
OCH2CONH2
H
OCH2C6H5
H


390.
OCH2CONH2
H
OCH2C6H5
CH3


391.
OCH2CONH2
H
OCH2C6H5
CO2CH2CH3


392.
OCH2CONH2
H
OCH2C6H5
CO2H


393.
OCH2CONH2
H
OCH2C6H5
CH2CO2CH2CH3


394.
OCH2CONH2
H
OCH2C6H5
CH2CO2H


395.
OCH2CONH2
H
OCH2C6H5
CH2CH2CO2CH2CH3


396.
OCH2CONH2
H
OCH2C6H5
CH2CH2CO2H


397.
OCH2CONH2
H
OCH2C6H5
CH2CH═CHCO2H


398.
OCH2CONH2
H
OCH2C6H5
CH2CH═CHCO2H


399.
OCH2CONH2
H
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


400.
OCH2CONH2
H
OCH2C6H5
CH2CH2P—O(OH)2


401.
OH
CH2N(CH3)2
OCH2C6H5
CO2CH2CH3


402.
OH
CH2N(CH3)2
OCH2C6H5
CO2H


403.
OH
CH2N(CH3)2
OCH2C6H5
CH2CO2CH2CH3


404.
OH
CH2N(CH3)2
OCH2C6H5
CH2CO2H


405.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2CH2CH3


406.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2H


407.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


408.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


409.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


410.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OH)2


411.
OCH3
CH2N(CH3)2
OCH2C6H5
CO2CH2CH3


412.
OCH3
CH2N(CH3)2
OCH2C6H5
CO2H


413.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CO2CH2CH3


414.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CO2H


415.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2CH2CH3


416.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2H


417.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


418.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


419.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2P—






O(OCH2CH3)2


420.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OH)2


421.
OH
CH2N+(CH3)3
OCH2C6H5
H




Cl−




422.
OH
CH2N+(CH3)3
OCH2C6H5
CH3




Cl−




423.
OH
CH2N+(CH3)3
OCH2C6H5
CO2CH2CH3




Cl−




424.
OH
CH2N+(CH3)3
OCH2C6H5
CO2H




Cl−




425.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CO2CH2CH3




Cl−




426.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CO2H




Cl−




427.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH2CO2CH2CH3




Cl−




428.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH2CO2H




Cl−




429.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH═CHCO2H




Cl−




430.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH═CHCO2H




Cl−




431.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH2P—




Cl−

O(OCH2CH3)2


432.
OH
CH2N+(CH3)3
OCH2C6H5
CH2CH2P—O(OH)2




Cl−




433.
OCH3
CH2N+(CH3)3
OCH2C6H5
H




Cl−




434.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH3




Cl−




435.
OCH3
CH2N+(CH3)3
OCH2C6H5
CO2CH2CH3




Cl−




436.
OCH3
CH2N+(CH3)3
OCH2C6H5
CO2H




Cl−




437.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CO2CH2CH3




Cl−




438.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CO2H




Cl−




439.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH2CO2CH2CH3




Cl−




440.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH2CO2H




Cl−




441.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH═CHCO2H




Cl−




442.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH═CHCO2H




Cl−




443.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH2P—




Cl−

O(OCH2CH3)2


444.
OCH3
CH2N+(CH3)3
OCH2C6H5
CH2CH2P—O(OH)2




Cl−




445.
H
H
OCH2CH═CH2
CO2CH2CH3


446.
H
H
OCH2CH═CH2
CO2H


447.
H
H
OCH2CH═CH2
CH2CO2CH2CH3


448.
H
H
OCH2CH═CH2
CH2CO2H


449.
H
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


450.
H
H
OCH2CH═CH2
CH2CH2CO2H


451.
H
H
OCH2CH═CH2
CH2CH═CHCO2H


452.
H
H
OCH2CH═CH2
CH2CH═CHCO2H


453.
H
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


454.
H
H
OCH2CH═CH2
CH2CH2P—O(OH)2


455.
OH
H
OCH2CH═CH2
CO2CH2CH3


456.
OH
H
OCH2CH═CH2
CO2H


457.
OH
H
OCH2CH═CH2
CH2CO2CH2CH3


458.
OH
H
OCH2CH═CH2
CH2CO2H


459.
OH
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


460.
OH
H
OCH2CH═CH2
CH2CH2CO2H


461.
OH
H
OCH2CH═CH2
CH2CH═CHCO2H


462.
OH
H
OCH2CH═CH2
CH2CH═CHCO2H


463.
OH
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


464.
OH
H
OCH2CH═CH2
CH2CH2P—O(OH)2


465.
OCH3
H
OCH2CH═CH2
CO2CH2CH3


466.
OCH3
H
OCH2CH═CH2
CO2H


467.
OCH3
H
OCH2CH═CH2
CH2CO2CH2CH3


468.
OCH3
H
OCH2CH═CH2
CH2CO2H


469.
OCH3
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


470.
OCH3
H
OCH2CH═CH2
CH2CH2CO2H


471.
OCH3
H
OCH2CH═CH2
CH2CH═CHCO2H


472.
OCH3
H
OCH2CH═CH2
CH2CH═CHCO2H


473.
OCH3
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


474.
OCH3
H
OCH2CH═CH2
CH2CH2P—O(OH)2


475.
OCH2CH═CH2
H
OCH2CH═CH2
CO2CH2CH3


476.
OCH2CH═CH2
H
OCH2CH═CH2
CO2H


477.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CO2CH2CH3


478.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CO2H


479.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


480.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2CO2H


481.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH═CHCO2H


482.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH═CHCO2H


483.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


484.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


485.
OCH2C6H5
H
OCH2CH═CH2
CO2CH2CH3


486.
OCH2C6H5
H
OCH2CH═CH2
CO2H


487.
OCH2C6H5
H
OCH2CH═CH2
CH2CO2CH2CH3


488.
OCH2C6H5
H
OCH2CH═CH2
CH2CO2H


489.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


490.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2CO2H


491.
OCH2C6H5
H
OCH2CH═CH2
CH2CH═CHCO2H


492.
OCH2C6H5
H
OCH2CH═CH2
CH2CH═CHCO2H


493.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


494.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2P—O(OH)2


495.
Cll
H
OCH2CH═CH2
CO2CH2CH3


496.
Cl
H
OCH2CH═CH2
CO2H


497.
Cl
H
OCH2CH═CH2
CH2CO2CH2CH3


498.
Cl
H
OCH2CH═CH2
CH2CO2H


499.
Cl
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


500.
Cl
H
OCH2CH═CH2
CH2CH2CO2H


501.
Cl
H
OCH2CH═CH2
CH2CH═CHCO2H


502.
Cl
H
OCH2CH═CH2
CH2CH═CHCO2H


503.
Cl
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


504.
Cl
H
OCH2CH═CH2
CH2CH2P—O(OH)2


505.
NO2
H
OCH2CH═CH2
CO2CH2CH3


506.
NO2
H
OCH2CH═CH2
CO2H


507.
NO2
H
OCH2CH═CH2
CH2CO2CH2CH3


508.
NO2
H
OCH2CH═CH2
CH2CO2H


509.
NO2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


510.
NO2
H
OCH2CH═CH2
CH2CH2CO2H


511.
NO2
H
OCH2CH═CH2
CH2CH═CHCO2H


512.
NO2
H
OCH2CH═CH2
CH2CH═CHCO2H


513.
NO2
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


514.
NO2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


515.
NH2
H
OCH2CH═CH2
CO2CH2CH3


516.
NH2
H
OCH2CH═CH2
CO2H


517.
NH2
H
OCH2CH═CH2
CH2CO2CH2CH3


518.
NH2
H
OCH2CH═CH2
CH2CO2H


519.
NH2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


520.
NH2
H
OCH2CH═CH2
CH2CH2CO2H


521.
NH2
H
OCH2CH═CH2
CH2CH═CHCO2H


522.
NH2
H
OCH2CH═CH2
CH2CH═CHCO2H


523.
NH2
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


524.
NH2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


525.
NHSO2CH3
H
OCH2CH═CH2
H


526.
NHSO2CH3
H
OCH2CH═CH2
CH3


527.
NHSO2CH3
H
OCH2CH═CH2
CO2CH2CH3


528.
NHSO2CH3
H
OCH2CH═CH2
CO2H


529.
NHSO2CH3
H
OCH2CH═CH2
CH2CO2CH2CH3


530.
NHSO2CH3
H
OCH2CH═CH2
CH2CO2H


531.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


532.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2CO2H


533.
NHSO2CH3
H
OCH2CH═CH2
CH2CH═CHCO2H


534.
NHSO2CH3
H
OCH2CH═CH2
CH2CH═CHCO2H


535.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


536.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2P—O(OH)2


537.
OCH2CONH2
H
OCH2CH═CH2
H


538.
OCH2CONH2
H
OCH2CH═CH2
CH3


539.
OCH2CONH2
H
OCH2CH═CH2
CO2CH2CH3


540.
OCH2CONH2
H
OCH2CH═CH2
CO2H


541.
OCH2CONH2
H
OCH2CH═CH2
CH2CO2CH2CH3


542.
OCH2CONH2
H
OCH2CH═CH2
CH2CO2H


543.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


544.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2CO2H


545.
OCH2CONH2
H
OCH2CH═CH2
CH2CH═CHCO2H


546.
OCH2CONH2
H
OCH2CH═CH2
CH2CH═CHCO2H


547.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


548.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


549.
OH
CH2N(CH3)2
OCH2CH═CH2
CO2CH2CH3


550.
OH
CH2N(CH3)2
OCH2CH═CH2
CO2H


551.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CO2CH2CH3


552.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CO2H


553.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2CH2CH3


554.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2H


555.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


556.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


557.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


558.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OH)2


559.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CO2CH2CH3


560.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CO2H


561.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CO2CH2CH3


562.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CO2H


563.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2CH2CH3


564.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2H


565.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


566.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


567.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—






O(OCH2CH3)2


568.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OH)2


569.
OH
CH2N+(CH3)3
OCH2CH═CH2
H




Cl−




570.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH3




Cl−




571.
OH
CH2N+(CH3)3
OCH2CH═CH2
CO2CH2CH3




Cl−




572.
OH
CH2N+(CH3)3
OCH2CH═CH2
CO2H




Cl−




573.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2CH2CH3




Cl−




574.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2H




Cl−




575.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2CH2CH3




Cl−




576.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2H




Cl−




577.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




578.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




579.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—




Cl−

O(OCH2CH3)2


580.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—O(OH)2




Cl−




581.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
H




Cl−




582.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH3




Cl−




583.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CO2CH2CH3




Cl−




584.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CO2H




Cl−




585.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2CH2CH3




Cl−




586.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2H




Cl−




587.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2CH2CH3




Cl−




588.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2H




Cl−




589.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




590.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




591.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—




Cl−

O(OCH2CH3)2


592.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—O(OH)2




Cl−




593.
H
H
OCH2CONH2
H


594.
H
H
OCH2CONH2
CH3


595.
H
H
OCH2CONH2
CO2CH2CH3


596.
H
H
OCH2CONH2
CO2H


597.
H
H
OCH2CONH2
CH2CO2CH2CH3


598.
H
H
OCH2CONH2
CH2CO2H


599.
H
H
OCH2CONH2
CH2CH2CO2CH2CH3


600.
H
H
OCH2CONH2
CH2CH2CO2H


601.
H
H
OCH2CONH2
CH2CH═CHCO2H


602.
H
H
OCH2CONH2
CH2CH═CHCO2H


603.
H
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


604.
H
H
OCH2CONH2
CH2CH2P—O(OH)2


605.
OH
H
OCH2CONH2
H


606.
OH
H
OCH2CONH2
CH3


607.
OH
H
OCH2CONH2
CO2CH2CH3


608.
OH
H
OCH2CONH2
CO2H


609.
OH
H
OCH2CONH2
CH2CO2CH2CH3


610.
OH
H
OCH2CONH2
CH2CO2H


611.
OH
H
OCH2CONH2
CH2CH2CO2CH2CH3


612.
OH
H
OCH2CONH2
CH2CH2CO2H


613.
OH
H
OCH2CONH2
CH2CH═CHCO2H


614.
OH
H
OCH2CONH2
CH2CH═CHCO2H


615.
OH
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


616.
OH
H
OCH2CONH2
CH2CH2P—O(OH)2


617.
OCH3
H
OCH2CONH2
H


618.
OCH3
H
OCH2CONH2
CH3


619.
OCH3
H
OCH2CONH2
CO2CH2CH3


620.
OCH3
H
OCH2CONH2
CO2H


621.
OCH3
H
OCH2CONH2
CH2CO2CH2CH3


622.
OCH3
H
OCH2CONH2
CH2CO2H


623.
OCH3
H
OCH2CONH2
CH2CH2CO2CH2CH3


624.
OCH3
H
OCH2CONH2
CH2CH2CO2H


625.
OCH3
H
OCH2CONH2
CH2CH═CHCO2H


626.
OCH3
H
OCH2CONH2
CH2CH═CHCO2H


627.
OCH3
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


628.
OCH3
H
OCH2CONH2
CH2CH2P—O(OH)2


629.
OCH2CH═CH2
H
OCH2CONH2
H


630.
OCH2CH═CH2
H
OCH2CONH2
CH3


631.
OCH2CH═CH2
H
OCH2CONH2
CO2CH2CH3


632.
OCH2CH═CH2
H
OCH2CONH2
CO2H


633.
OCH2CH═CH2
H
OCH2CONH2
CH2CO2CH2CH3


634.
OCH2CH═CH2
H
OCH2CONH2
CH2CO2H


635.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2CO2CH2CH3


636.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2CO2H


637.
OCH2CH═CH2
H
OCH2CONH2
CH2CH═CHCO2H


638.
OCH2CH═CH2
H
OCH2CONH2
CH2CH═CHCO2H


639.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


640.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2P—O(OH)2


641.
OCH2C6H5
H
OCH2CONH2
H


642.
OCH2C6H5
H
OCH2CONH2
CH3


643.
OCH2C6H5
H
OCH2CONH2
CO2CH2CH3


644.
OCH2C6H5
H
OCH2CONH2
CO2H


645.
OCH2C6H5
H
OCH2CONH2
CH2CO2CH2CH3


646.
OCH2C6H5
H
OCH2CONH2
CH2CO2H


647.
OCH2C6H5
H
OCH2CONH2
CH2CH2CO2CH2CH3


648.
OCH2C6H5
H
OCH2CONH2
CH2CH2CO2H


649.
OCH2C6H5
H
OCH2CONH2
CH2CH═CHCO2H


650.
OCH2C6H5
H
OCH2CONH2
CH2CH═CHCO2H


651.
OCH2C6H5
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


652.
OCH2C6H5
H
OCH2CONH2
CH2CH2P—O(OH)2


653.
Cl
H
OCH2CONH2
H


654.
Cl
H
OCH2CONH2
CH3


655.
Cl
H
OCH2CONH2
CO2CH2CH3


656.
Cl
H
OCH2CONH2
CO2H


657.
Cl
H
OCH2CONH2
CH2CO2CH2CH3


658.
Cl
H
OCH2CONH2
CH2CO2H


659.
Cl
H
OCH2CONH2
CH2CH2CO2CH2CH3


660.
Cl
H
OCH2CONH2
CH2CH2CO2H


661.
Cl
H
OCH2CONH2
CH2CH═CHCO2H


662.
Cl
H
OCH2CONH2
CH2CH═CHCO2H


663.
Cl
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


664.
Cl
H
OCH2CONH2
CH2CH2P—O(OH)2


665.
NO2
H
OCH2CONH2
H


666.
NO2
H
OCH2CONH2
CH3


667.
NO2
H
OCH2CONH2
CO2CH2CH3


668.
NO2
H
OCH2CONH2
CO2H


669.
NO2
H
OCH2CONH2
CH2CO2CH2CH3


670.
NO2
H
OCH2CONH2
CH2CO2H


671.
NO2
H
OCH2CONH2
CH2CH2CO2CH2CH3


672.
NO2
H
OCH2CONH2
CH2CH2CO2H


673.
NO2
H
OCH2CONH2
CH2CH═CHCO2H


674.
NO2
H
OCH2CONH2
CH2CH═CHCO2H


675.
NO2
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


676.
NO2
H
OCH2CONH2
CH2CH2P—O(OH)2


677.
NH2
H
OCH2CONH2
H


678.
NH2
H
OCH2CONH2
CH3


679.
NH2
H
OCH2CONH2
CO2CH2CH3


680.
NH2
H
OCH2CONH2
CO2H


681.
NH2
H
OCH2CONH2
CH2CO2CH2CH3


682.
NH2
H
OCH2CONH2
CH2CO2H


683.
NH2
H
OCH2CONH2
CH2CH2CO2CH2CH3


684.
NH2
H
OCH2CONH2
CH2CH2CO2H


685.
NH2
H
OCH2CONH2
CH2CH═CHCO2H


686.
NH2
H
OCH2CONH2
CH2CH═CHCO2H


687.
NH2
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


688.
NH2
H
OCH2CONH2
CH2CH2P—O(OH)2


689.
NHSO2CH3
H
OCH2CONH2
H


690.
NHSO2CH3
H
OCH2CONH2
CH3


691.
NHSO2CH3
H
OCH2CONH2
CO2CH2CH3


692.
NHSO2CH3
H
OCH2CONH2
CO2H


693.
NHSO2CH3
H
OCH2CONH2
CH2CO2CH2CH3


694.
NHSO2CH3
H
OCH2CONH2
CH2CO2H


695.
NHSO2CH3
H
OCH2CONH2
CH2CH2CO2CH2CH3


696.
NHSO2CH3
H
OCH2CONH2
CH2CH2CO2H


697.
NHSO2CH3
H
OCH2CONH2
CH2CH═CHCO2H


698.
NHSO2CH3
H
OCH2CONH2
CH2CH═CHCO2H


699.
NHSO2CH3
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


700.
NHSO2CH3
H
OCH2CONH2
CH2CH2P—O(OH)2


701.
OCH2CONH2
H
OCH2CONH2
H


702.
OCH2CONH2
H
OCH2CONH2
CH3


703.
OCH2CONH2
H
OCH2CONH2
CO2CH2CH3


704.
OCH2CONH2
H
OCH2CONH2
CO2H


705.
OCH2CONH2
H
OCH2CONH2
CH2CO2CH2CH3


706.
OCH2CONH2
H
OCH2CONH2
CH2CO2H


707.
OCH2CONH2
H
OCH2CONH2
CH2CH2CO2CH2CH3


708.
OCH2CONH2
H
OCH2CONH2
CH2CH2CO2H


709.
OCH2CONH2
H
OCH2CONH2
CH2CH═CHCO2H


710.
OCH2CONH2
H
OCH2CONH2
CH2CH═CHCO2H


711.
OCH2CONH2
H
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


712.
OCH2CONH2
H
OCH2CONH2
CH2CH2P—O(OH)2


713.
OH
CH2N(CH3)2
OCH2CONH2
H


714.
OH
CH2N(CH3)2
OCH2CONH2
CH3


715.
OH
CH2N(CH3)2
OCH2CONH2
CO2CH2CH3


716.
OH
CH2N(CH3)2
OCH2CONH2
CO2H


717.
OH
CH2N(CH3)2
OCH2CONH2
CH2CO2CH2CH3


718.
OH
CH2N(CH3)2
OCH2CONH2
CH2CO2H


719.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2CH2CH3


720.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2H


721.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


722.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


723.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


724.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OH)2


725.
OCH3
CH2N(CH3)2
OCH2CONH2
H


726.
OCH3
CH2N(CH3)2
OCH2CONH2
CH3


727.
OCH3
CH2N(CH3)2
OCH2CONH2
CO2CH2CH3


728.
OCH3
CH2N(CH3)2
OCH2CONH2
CO2H


729.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CO2CH2CH3


730.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CO2H


731.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2CH2CH3


732.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2H


733.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


734.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


735.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2P—






O(OCH2CH3)2


736.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OH)2


737.
OH
CH2N+(CH3)3
OCH2CONH2
H




Cl−




738.
OH
CH2N+(CH3)3
OCH2CONH2
CH3




Cl−




739.
OH
CH2N+(CH3)3
OCH2CONH2
CO2CH2CH3




Cl−




740.
OH
CH2N+(CH3)3
OCH2CONH2
CO2H




Cl−




741.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CO2CH2CH3




Cl−




742.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CO2H




Cl−




743.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2CH2CH3




Cl−




744.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2H




Cl−




745.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




746.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




747.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—




Cl−

O(OCH2CH3)2


748.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—O(OH)2




Cl−




749.
OCH3
CH2N+(CH3)3
OCH2CONH2
H




Cl−




750.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH3




Cl−




751.
OCH3
CH2N+(CH3)3
OCH2CONH2
CO2CH2CH3




Cl−




752.
OCH3
CH2N+(CH3)3
OCH2CONH2
CO2H




Cl−




753.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CO2CH2CH3




Cl−




754.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CO2H




Cl−




755.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2CH2CH3




Cl−




756.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2H




Cl−




757.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




758.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




759.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—




Cl−
O(OCH2CH3)2



760.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—O(OH)2




Cl−




761.
H
H
H
CH2-tetrazole


762.
OCH3
H
H
CH2-tetrazole


763.
OCH2C6H5
H
H
CH2-tetrazole
















TABLE VI













Cl is present when Q is other than O.


 










Ex. #
X
Q
R1













1.
H
CH3
H


2.
H
CH2CH═CH2
H


3.
H
CH2C≡CH
H


4.
H
O−
H


5.
H
CH3
CH3


6.
H
CH2CH═CH2
CH3


7.
H
CH2C≡CH
CH3


8.
H
O−
CH3


9.
H
CH3
CH2CO2CH2CH3


10.
H
CH2CH═CH2
CH2CO2CH2CH3


11.
H
CH2C≡CH
CH2CO2CH2CH3


12.
H
O−
CH2CO2CH2CH3


13.
H
CH3
CH2CH2PO(OCH2CH3)2


14.
H
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


15.
H
CH2C≡CH
CH2CH2PO(OCH2CH3)2


16.
H
O−
CH2CH2PO(OCH2CH3)2


17.
OH
CH3
H


18.
OH
CH2CH═CH2
H


19.
OH
CH2C≡CH
H


20.
OH
O−
H


21.
OH
CH3
CH3


22.
OH
CH2CH═CH2
CH3


23.
OH
CH2C≡CH
CH3


24.
OH
O−
CH3


25.
OH
CH3
CH2CO2CH2CH3


26.
OH
CH2CH═CH2
CH2CO2CH2CH3


27.
OH
CH2C≡CH
CH2CO2CH2CH3


28.
OH
O−
CH2CO2CH2CH3


29.
OH
CH3
CH2CH2PO(OCH2CH3)2


30.
OH
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


31.
OH
CH2C≡CH
CH2CH2PO(OCH2CH3)2


32.
OH
O−
CH2CH2PO(OCH2CH3)2


33.
OCH3
CH3
H


34.
OCH3
CH2CH═CH2
H


35.
OCH3
CH2C≡CH
H


36.
OCH3
O−
H


37.
OCH3
CH3
CH3


38.
OCH3
CH2CH═CH2
CH3


39.
OCH3
CH2C≡CH
CH3


40.
OCH3
O−
CH3


41.
OCH3
CH3
CH2CO2CH2CH3


42.
OCH3
CH2CH═CH2
CH2CO2CH2CH3


43.
OCH3
CH2C≡CH
CH2CO2CH2CH3


44.
OCH3
O−
CH2CO2CH2CH3


45.
OCH3
CH3
CH2CH2PO(OCH2CH3)2


46.
OCH3
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


47.
OCH3
CH2C≡CH
CH2CH2PO(OCH2CH3)2


48.
OCH3
O−
CH2CH2PO(OCH2CH3)2


49.
Cl
CH3
H


50.
Cl
CH2CH═CH2
H


51.
Cl
CH2C≡CH
H


52.
Cl
O−
H


53.
Cl
CH3
CH3


54.
Cl
CH2CH═CH2
CH3


55.
Cl
CH2C≡CH
CH3


56.
Cl
O−
CH3


57.
Cl
CH3
CH2CO2CH2CH3


58.
Cl
CH2CH═CH2
CH2CO2CH2CH3


59.
Cl
CH2C≡CH
CH2CO2CH2CH3


60.
Cl
O−
CH2CO2CH2CH3


61.
Cl
CH3
CH2CH2PO(OCH2CH3)2


62.
Cl
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


63.
Cl
CH2C≡CH
CH2CH2PO(OCH2CH3)2


64.
Cl
O−
CH2CH2PO(OCH2CH3)2


65.
NO2
CH3
H


66.
NO2
CH2CH═CH2
H


67.
NO2
CH2C≡CH
H


68.
NO2
O−
H


69.
NO2
CH3
CH3


70.
NO2
CH2CH═CH2
CH3


71.
NO2
CH2C≡CH
CH3


72.
NO2
O−
CH3


73.
NO2
CH3
CH2CO2CH2CH3


74.
NO2
CH2CH═CH2
CH2CO2CH2CH3


75.
NO2
CH2C≡CH
CH2CO2CH2CH3


76.
NO2
O−
CH2CO2CH2CH3


77.
NO2
CH3
CH2CH2PO(OCH2CH3)2


78.
NO2
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


79.
NO2
CH2C≡CH
CH2CH2PO(OCH2CH3)2


80.
NO2
O−
CH2CH2PO(OCH2CH3)2


81.
NH2
CH3
H


82.
NH2
CH2CH═CH2
H


83.
NH2
CH2C≡CH
H


84.
NH2
O−
H


85.
NH2
CH3
CH3


86.
NH2
CH2CH═CH2
CH3


87.
NH2
CH2C≡CH
CH3


88.
NH2
O−
CH3


89.
NH2
CH3
CH2CO2CH2CH3


90.
NH2
CH2CH═CH2
CH2CO2CH2CH3


91.
NH2
CH2C≡CH
CH2CO2CH2CH3


92.
NH2
O−
CH2CO2CH2CH3


93.
NH2
CH3
CH2CH2PO(OCH2CH3)2


94.
NH2
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


95.
NH2
CH2C≡CH
CH2CH2PO(OCH2CH3)2


96.
NH2
O−
CH2CH2PO(OCH2CH3)2


97.
NHSO2CH3
CH3
H


98.
NHSO2CH3
CH2CH═CH2
H


99.
NHSO2CH3
CH2C≡CH
H


100.
NHSO2CH3
O−
H


101.
NHSO2CH3
CH3
CH3


102.
NHSO2CH3
CH2CH═CH2
CH3


103.
NHSO2CH3
CH2C≡CH
CH3


104.
NHSO2CH3
O−
CH3


105.
NHSO2CH3
CH3
CH2CO2CH2CH3


106.
NHSO2CH3
CH2CH═CH2
CH2CO2CH2CH3


107.
NHSO2CH3
CH2C≡CH
CH2CO2CH2CH3


108.
NHSO2CH3
O−
CH2CO2CH2CH3


109.
NHSO2CH3
CH3
CH2CH2PO(OCH2CH3)2


110.
NHSO2CH3
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


111.
NHSO2CH3
CH2C≡CH
CH2CH2PO(OCH2CH3)2


112.
NHSO2CH3
O−
CH2CH2PO(OCH2CH3)2


113.
OCH2C6H5
CH3
H


114.
OCH2C6H5
CH2CH═CH2
H


115.
OCH2C6H5
CH2C≡CH
H


116.
OCH2C6H5
O−
H


117.
OCH2C6H5
CH3
CH3


118.
OCH2C6H5
CH2CH═CH2
CH3


119.
OCH2C6H5
CH2C≡CH
CH3


120.
OCH2C6H5
O−
CH3


121.
OCH2C6H5
CH3
CH2CO2CH2CH3


122.
OCH2C6H5
CH2CH═CH2
CH2CO2CH2CH3


123.
OCH2C6H5
CH2C≡CH
CH2CO2CH2CH3


124.
OCH2C6H5
O−
CH2CO2CH2CH3


125.
OCH2C6H5
CH3
CH2CH2PO(OCH2CH3)2


126.
OCH2C6H5
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


127.
OCH2C6H5
CH2C≡CH
CH2CH2PO(OCH2CH3)2


128.
OCH2C6H5
O−
CH2CH2PO(OCH2CH3)2


129.
OCH2CH2C6H5
CH3
H


130.
OCH2CH2C6H5
CH2CH═CH2
H


131.
OCH2CH2C6H5
CH2C≡CH
H


132.
OCH2CH2C6H5
O−
H


133.
OCH2CH2C6H5
CH3
CH3


134.
OCH2CH2C6H5
CH2CH═CH2
CH3


135.
OCH2CH2C6H5
CH2C≡CH CH3



136.
OCH2CH2C6H5
O−
CH3


137.
OCH2C6H4—Cl
CH3
H



2, 3, or 4




138.
OCH2C6H4—Cl
CH2CH═CH2
H



2, 3, or 4




139.
OCH2C6H4—Cl
CH2CCH
H



2, 3, or 4




140.
OCH2C6H4—Cl
O−
H



2, 3, or 4




141.
OCH2C6H4—Cl
CH3
CH3



2, 3, or 4




142.
OCH2C6H4—Cl
CH2CH═CH2
CH3



2, 3, or 4




143.
OCH2C6H4—Cl
CH2C≡CH
CH3



2, 3, or 4




144.
OCH2C6H4—Cl
O−
CH3



2, 3, or 4




145.
OCH2C6H4OCH3
CH3
H



2, 3, or 4




146.
OCH2C6H4OCH3
CH2CH═CH2
H



2, 3, or 4




147.
OCH2C6H4OCH3
CH2C≡CH H




2, 3, or 4




148.
OCH2C6H4OCH3
O−
H



2, 3, or 4




149.
OCH2C6H4OCH3
CH3
CH3



2, 3, or 4




150.
OCH2C6H4OCH3
CH2CH═CH2
CH3



(2, 3, or 4)




151.
OCH2C6H4OCH3
CH2C≡CH CH3




2, 3, or 4




152.
OCH2C6H4OCH3
O−
CH3



2, 3, or 4




153.
OCH2C6H4C6H5
CH3
H


154.
OCH2C6H4C6H5
CH2CH═CH2
H


155.
OCH2C6H4C6H5
CH2C≡CH H



156.
OCH2C6H4C6H5
O−
H


157.
OCH2C6H4C6H5
CH3
CH3


158.
OCH2C6H4C6H5
CH2CH═CH2
CH3


159.
OCH2C6H4C6H5
CH2C≡CH CH3



160.
OCH2C6H4C6H5
O−
CH3
















TABLE VII













Cl is present when Q is other than O.


 










Ex. #
X
Q
R1













1.
H
CH3
H


2.
H
CH2CH═CH2
H


3.
H
CH2C≡CH
H


4.
H
O−
H


5.
H
CH3
CH3


6.
H
CH2CH═CH2
CH3


7.
H
CH2C≡CH
CH3


8.
H
O−
CH3


9.
H
CH3
CH2CO2CH2CH3


10.
H
CH2CH═CH2
CH2CO2CH2CH3


11.
H
CH2C≡CH
CH2CO2CH2CH3


12.
H
O−
CH2CO2CH2CH3


13.
H
CH3
CH2CH2PO(OCH2CH3)2


14.
H
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


15.
H
CH2C≡CH
CH2CH2PO(OCH2CH3)2


16.
H
O−
CH2CH2PO(OCH2CH3)2


17.
OH
CH3
H


18.
OH
CH2CH═CH2
H


19.
OH
CH2C≡CH
H


20.
OH
O−
H


21.
OH
CH3
CH3


22.
OH
CH2CH═CH2
CH3


23.
OH
CH2C≡CH
CH3


24.
OH
O−
CH3


25.
OH
CH3
CH2CO2CH2CH3


26.
OH
CH2CH═CH2
CH2CO2CH2CH3


27.
OH
CH2C≡CH
CH2CO2CH2CH3


28.
OH
O−
CH2CO2CH2CH3


29.
OH
CH3
CH2CH2PO(OCH2CH3)2


30.
OH
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


31.
OH
CH2C≡CH
CH2CH2PO(OCH2CH3)2


32.
OH
O−
CH2CH2PO(OCH2CH3)2


33.
OCH3
CH3
H


34.
OCH3
CH2CH═CH2
H


35.
OCH3
CH2C≡CH
H


36.
OCH3
O−
H


37.
OCH3
CH3
CH3


38.
OCH3
CH2CH═CH2
CH3


39.
OCH3
CH2C≡CH
CH3


40.
OCH3
O−
CH3


41.
OCH3
CH3
CH2CO2CH2CH3


42.
OCH3
CH2CH═CH2
CH2CO2CH2CH3


43.
OCH3
CH2C≡CH
CH2CO2CH2CH3


44.
OCH3
O−
CH2CO2CH2CH3


45.
OCH3
CH3
CH2CH2PO(OCH2CH3)2


46.
OCH3
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


47.
OCH3
CH2C≡CH
CH2CH2PO(OCH2CH3)2


48.
OCH3
O−
CH2CH2PO(OCH2CH3)2


49.
Cl
CH3
H


50.
Cl
CH2CH═CH2
H


51.
Cl
CH2C≡CH
H


52.
Cl
O−
H


53.
Cl
CH3
CH3


54.
Cl
CH2CH═CH2
CH3


55.
Cl
CH2C≡CH
CH3


56.
Cl
O−
CH3


57.
Cl
CH3
CH2CO2CH2CH3


58.
Cl
CH2CH═CH2
CH2CO2CH2CH3


59.
Cl
CH2C≡CH
CH2CO2CH2CH3


60.
Cl
O−
CH2CO2CH2CH3


61.
Cl
CH3
CH2CH2PO(OCH2CH3)2


62.
Cl
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


63.
Cl
CH2C≡CH
CH2CH2PO(OCH2CH3)2


64.
Cl
O−
CH2CH2PO(OCH2CH3)2


65.
NO2
CH3
H


66.
NO2
CH2CH═CH2
H


67.
NO2
CH2C≡CH
H


68.
NO2
O−
H


69.
NO2
CH3
CH3


70.
NO2
CH2CH═CH2
CH3


71.
NO2
CH2C≡CH
CH3


72.
NO2
O−
CH3


73.
NO2
CH3
CH2CO2CH2CH3


74.
NO2
CH2CH═CH2
CH2CO2CH2CH3


75.
NO2
CH2C≡CH
CH2CO2CH2CH3


76.
NO2
O−
CH2CO2CH2CH3


77.
NO2
CH3
CH2CH2PO(OCH2CH3)2


78.
NO2
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


79.
NO2
CH2C≡CH
CH2CH2PO(OCH2CH3)2


80.
NO2
O−
CH2CH2PO(OCH2CH3)2


81.
NH2
CH3
H


82.
NH2
CH2CH═CH2
H


83.
NH2
CH2C≡CH
H


84.
NH2
O−
H


85.
NH2
CH3
CH3


86.
NH2
CH2CH═CH2
CH3


87.
NH2
CH2C≡CH
CH3


88.
NH2
O−
CH3


89.
NH2
CH3
CH2CO2CH2CH3


90.
NH2
CH2CH═CH2
CH2CO2CH2CH3


91.
NH2
CH2C≡CH
CH2CO2CH2CH3


92.
NH2
O−
CH2CO2CH2CH3


93.
NH2
CH3
CH2CH2PO(OCH2CH3)2


94.
NH2
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


95.
NH2
CH2C≡CH
CH2CH2PO(OCH2CH3)2


96.
NH2
O−
CH2CH2PO(OCH2CH3)2


97.
NHSO2CH3
CH3
H


98.
NHSO2CH3
CH2CH═CH2
H


99.
NHSO2CH3
CH2C≡CH
H


100.
NHSO2CH3
O−
H


101.
NHSO2CH3
CH3
CH3


102.
NHSO2CH3
CH2CH═CH2
CH3


103.
NHSO2CH3
CH2C≡CH
CH3


104.
NHSO2CH3
O−
CH3


105.
NHSO2CH3
CH3
CH2CO2CH2CH3


106.
NHSO2CH3
CH2CH═CH2
CH2CO2CH2CH3


107.
NHSO2CH3
CH2C≡CH
CH2CO2CH2CH3


108.
NHSO2CH3
O−
CH2CO2CH2CH3


109.
NHSO2CH3
CH3
CH2CH2PO(OCH2CH3)2


110.
NHSO2CH3
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


111.
NHSO2CH3
CH2C≡CH
CH2CH2PO(OCH2CH3)2


112.
NHSO2CH3
O−
CH2CH2PO(OCH2CH3)2


113.
OCH2C6H5
CH3
H


114.
OCH2C6H5
CH2CH═CH2
H


115.
OCH2C6H5
CH2C≡CH
H


116.
OCH2C6H5
O−
H


117.
OCH2C6H5
CH3
CH3


118.
OCH2C6H5
CH2CH═CH2
CH3


119.
OCH2C6H5
CH2C≡CH
CH3


120.
OCH2C6H5
O−
CH3


121.
OCH2C6H5
CH3
CH2CO2CH2CH3


122.
OCH2C6H5
CH2CH═CH2
CH2CO2CH2CH3


123.
OCH2C6H5
CH2C≡CH
CH2CO2CH2CH3


124.
OCH2C6H5
O−
CH2CO2CH2CH3


125.
OCH2C6H5
CH3
CH2CH2PO(OCH2CH3)2


126.
OCH2C6H5
CH2CH═CH2
CH2CH2PO(OCH2CH3)2


127.
OCH2C6H5
CH2C≡CH
CH2CH2PO(OCH2CH3)2


128.
OCH2C6H5
O−
CH2CH2PO(OCH2CH3)2


129.
OCH2CH2C6H5
CH3
H


130.
OCH2CH2C6H5
CH2CH═CH2
H


131.
OCH2CH2C6H5
CH2C≡CH
H


132.
OCH2CH2C6H5
O−
H


133.
OCH2CH2C6H5
CH3
CH3


134.
OCH2CH2C6H5
CH2CH═CH2
CH3


135.
OCH2CH2C6H5
CH2C≡CH
CH3


136.
OCH2CH2C6H5
O−
CH3


137.
OCH2C6H4—2-Cl
CH3
H


138.
OCH2C6H4—3-Cl
CH3
H


139.
OCH2C6H4—4-Cl
CH3
H


140.
OCH2C6H4—2-Cl
CH2CH═CH2
H


141.
OCH2C6H4—3-Cl
CH2CH═CH2
H


142.
OCH2C6H4—4-Cl
CH2CH═CH2
H


143.
OCH2C6H4—2-Cl
CH2C≡CH
H


144.
OCH2C6H4—3-Cl
CH2C≡CH
H


145.
OCH2C6H4—4-Cl
CH2C≡CH
H


146.
OCH2C6H4—2-Cl
O−
H


147.
OCH2C6H4—3-Cl
O−
H


148.
OCH2C6H4—4-Cl
O−
H


149.
OCH2C6H4—2-Cl
CH3
CH3


150.
OCH2C6H4—3-Cl
CH3
CH3


151.
OCH2C6H4—4-Cl
CH3
CH3


152.
OCH2C6H4—2-Cl
CH2CH═CH2
CH3


153.
OCH2C6H4—3-Cl
CH2CH═CH2
CH3


154.
OCH2C6H4—4-Cl
CH2CH═CH2
CH3


155.
OCH2C6H4—2-Cl
CH2C≡CH
CH3


156.
OCH2C6H4—3-Cl
CH2C≡CH
CH3


157.
OCH2C6H4—4-Cl
CH2C≡CH
CH3


158.
OCH2C6H4—2-Cl
O−
CH3


159.
OCH2C6H4—3-Cl
O−
CH3


160.
OCH2C6H4—4-Cl
O−
CH3


161.
OCH2C6H4—2-
CH3
H



OCH3




162.
OCH2C6H4—3-
CH3
H



OCH3




163.
OCH2C6H4—4-
CH3
H



OCH3




164.
OCH2C6H4—2-
CH2CH═CH2
H



OCH3




165.
OCH2C6H4—3-
CH2CH═CH2
H



OCH3




166.
OCH2C6H4—4-
CH2CH═CH2
H



OCH3




167.
OCH2C6H4—2-
CH2C≡CH
H



OCH3




168.
OCH2C6H4—3-
CH2C≡CH
H



OCH3




169.
OCH2C6H4—4-
CH2C≡CH
H



OCH3




170.
OCH2C6H4—2-
O−
H



OCH3




171.
OCH2C6H4—3-
O−
H



OCH3




172.
OCH2C6H4—4-
O−
H



OCH3




173.
OCH2C6H4—2-
CH3
CH3



OCH3




174.
OCH2C6H4—3-
CH3
CH3



OCH3




175.
OCH2C6H4—4-
CH3
CH3



OCH3




176.
OCH2C6H4—2-
CH2CH═CH2
CH3



OCH3




177.
OCH2C6H4—3-
CH2CH═CH2
CH3



OCH3




178.
OCH2C6H4—4-
CH2CH═CH2
CH3



OCH3




179.
OCH2C6H4—2-
CH2C≡CH
CH3



OCH3




180.
OCH2C6H4—3-
CH2C≡CH
CH3



OCH3




181.
OCH2C6H4—4-
CH2C≡CH
CH3



OCH3




182.
OCH2C6H4—2-
O−
CH3



OCH3




183.
OCH2C6H4—3-
O−
CH3



OCH3




184.
OCH2C6H4—4-
O−
CH3



OCH3




185.
OCH2C6H4C6H5
CH3
H


186.
OCH2C6H4C6H5
CH2CH═CH2
H


187.
OCH2C6H4C6H5
CH2C≡CH
H


188.
OCH2C6H4C6H5
O−
H


189.
OCH2C6H4C6H5
CH3
CH3


190.
OCH2C6H4C6H5
CH2CH═CH2
CH3


191.
OCH2C6H4C6H5
CH2C≡CH
CH3


192.
OCH2C6H4C6H5
O−
CH3
















TABLE VIIIa













 









Ex. #
X
R1












1.
NO2
H


2.
NO2
CH3


3.
CN
H


4.
CN
CH3


5.
CONH2
H


6.
CONH2
CH3


7.
CO2H
H


8.
CO2H
CH3


9.
NHSO2CH3
H


10.
NHSO2CH3
CH3


11.
OCH2C6H5
H


12.
OCH2C6H5
CH3


13.
OCH2C6H4C6H5
H


14.
OCH2C6H4C6H5
CH3


15.
OCH2CH2C6H5
H


16.
OCH2CH2C6H5
CH3


17.
OCH2C6H4Cl(2, 3, or 4)
H


18.
OCH2C6H4Cl(2, 3, or 4)
CH3


19.
OCH2C6H4OCH3(2, 3, or 4)
H


20.
OCH2C6H4OCH3(2, 3, or 4)
CH3


21.
OCH2C6H4F(2, 3, or 4)
H


22.
OCH2C6H4F(2, 3, or 4)
CH3


23.
OCH2C6H4CN(2, 3, or 4)
H


24.
OCH2C6H4CN(2, 3, or 4)
CH3


25.
OCH2C6H4CONH2(2, 3, or 4)
H


26.
OCH2C6H4CONH2(2, 3, or 4)
CH3


27.
OCH2C6H4CH2CN(2, 3, or 4)
H


28.
OCH2C6H4CH2CN(2, 3, or 4)
CH3


29.
OCH2C6H4CH2CONH2(2, 3, or 4)
H


30.
OCH2C6H4CH2CONH2(2, 3, or 4)
CH3


31.
OCH2C6H4OCH2CN(2, 3, or 4)
H


32.
OCH2C6H4OCH2CN(2, 3, or 4)
CH3


33.
OCH2C6H4OCH2CONH2(2, 3, or 4)
H


34.
OCH2C6H4OCH2CONH2(2, 3, or 4)
CH3


35.
OCH2C6H3(CN)2(3,5)
H


36.
OCH2C6H3(CN)2(3,5)
CH3


37.
OCH2C6H3(CONH2)2(3,5)
H


38.
OCH2C6H3(CONH2)2(3,5)
CH3


39.
OCH2C6H4—NO2(2, 3, or 4)
H


40.
OCH2C6H4—NO2(2, 3, or 4)
CH3


41.
OCH2C6H4—CF3(2, 3, or 4)
H


42.
OCH2C6H4—CF3(2, 3, or 4)
CH3


43.
OCH2C6H4—CH3(2, 3, or 4)
H


44.
OCH2C6H4—CH3(2, 3, or 4)
CH3


45.
OCH2C6H4—NHSO2CH3(2, 3, or 4)
H


46.
OCH2C6H4—NHSO2CH3(2, 3, or 4)
CH3


47.
OCH2C6H4C6H4CN(2, 3, or 4)
H


48.
OCH2C6H4C6H4CN(2, 3, or 4)
CH3


49.
OCH2C6H4C6H4CONH2(2, 3, or 4)
H


50.
OCH2C6H4C6H4CONH2(2, 3, or 4)
CH3


51.
OCH2C6H4C6H4CO2H(2, 3, or 4)
H


52.
OCH2C6H4C6H4CO2H(2, 3, or 4)
CH3
















TABLE VIIIb













 









Ex. #
X′
R1












1.
NO2
H


2.
NO2
CH3


3.
CN
H


4.
CN
CH3


5.
CONH2
H


6.
CONH2
CH3


7.
CO2H
H


8.
CO2H
CH3


9.
NHSO2CH3
H


10.
NHSO2CH3
CH3


11.
OCH2C6H5
H


12.
OCH2C6H5
CH3


13.
OCH2CH2C6H5
H


14.
OCH2C6H4C6H5
H


15.
OCH2C6H4C6H5
CH3


16.
OCH2CH2C6H5
CH3


17.
OCH2C6H4—Cl(2, 3, or 4)
H


18.
OCH2C6H4—Cl(2, 3, or 4)
CH3


19.
OCH2C6H4—OCH3(2, 3, or 4)
H


20.
OCH2C6H4—OCH3(2, 3, or 4)
CH3


21.
OCH2C6H4—F(2, 3, or 4)
H


22.
OCH2C6H4—F(2, 3, or 4)
CH3


23.
OCH2C6H4CN(2, 3, or 4)
H


24.
OCH2C6H4CN(2, 3, or 4)
CH3


25.
OCH2C6H4CONH2(2, 3, or 4)
H


26.
OCH2C6H4CONH2(2, 3, or 4)
CH3


27.
OCH2C6H4CH2CN(2, 3, or 4)
H


28.
OCH2C6H4CH2CN(2, 3, or 4)
CH3


29.
OCH2C6H4CH2CONH2(2, 3, or 4)
H


30.
OCH2C6H4CH2CONH2(2, 3, or 4)
CH3


31.
OCH2C6H4OCH2CN(2, 3, or 4)
H


32.
OCH2C6H4OCH2CN(2, 3, or 4)CH3



33.
OCH2C6H4OCH2CONH2(2, 3, or 4)
H


34.
OCH2C6H4OCH2CONH2(2, 3, or 4)
CH3


35.
OCH2C6H3(CN)2(3, 5)
H


36.
OCH2C6H3(CN)2(3, 5)
CH3


37.
OCH2C6H3(CONH2)2(3, 5)
H


38.
OCH2C6H3(CONH2)2(3, 5)
CH3


39.
OCH2C6H4—NO2(2, 3, or 4)
H


40.
OCH2C6H4—NO2(2, 3, or 4)
CH3


41.
OCH2C6H4—CF3(2, 3, or 4)
H


42.
OCH2C6H4—CF3(2, 3, or 4)
CH3


43.
OCH2C6H4—CH3(2, 3, or 4)
H


44.
OCH2C6H4—CH3(2, 3, or 4)
CH3


45.
OCH2C6H4—NHSO2CH3(2, 3, or 4)
H


46.
OCH2C6H4—NHSO2CH3(2, 3, or 4)
CH3


47.
OCH2C6H4C6H4CN(2, 3, or 4)
H


48.
OCH2C6H4C6H4CN(2, 3, or 4)
CH3


49.
OCH2C6H4C6H4CONH2(2, 3, or 4)
H


50.
OCH2C6H4C6H4CONH2(2, 3, or 4)
CH3


51.
OCH2C6H4C6H4CO2H(2, 3, or 4)
H


52.
OCH2C6H4C6H4CO2H(2, 3, or 4)
CH3
















TABLE VIIIc













 









Ex. #
X
R1












1.
NHCH2C6H5
H


2.
NHCH2C6H5
CH3


3.
NHCH2C6H4C6H5
H


4.
NHCH2C6H4C6H5
CH3


5.
NHCH2CH2C6H5
H


6.
NHCH2CH2C6H5
CH3


7.
NHCH2C6H4—Cl(2, 3, or 4)
H


8.
NHCH2C6H4—Cl(2, 3, or 4)
CH3


9.
NHCH2C6H4—OCH3(2, 3, or 4)
H


10.
NHCH2C6H4—OCH3(2, 3, or 4)
CH3


11.
NHCH2C6H4—F(2, 3, or 4)
H


12.
NHCH2C6H4—F(2, 3, or 4)
CH3


13.
NHCH2C6H4CN(2, 3, or 4)
H


14.
NHCH2C6H4CN(2, 3, or 4)
CH3


15.
NHCH2C6H4CONH2(2, 3, or 4)
H


16.
NHCH2C6H4CONH2(2, 3, or 4)
CH3


17.
NHCH2C6H4CH2CN(2, 3, or 4)
H


18.
NHCH2C6H4CH2CN(2, 3, or 4)
CH3


19.
NHCH2C6H4CH2CONH2(2, 3, or 4)
H


20.
NHCH2C6H4CH2CONH2(2, 3, or 4)
CH3


21.
NHCH2C6H4OCH2CN(2, 3, or 4)
H


22.
NHCH2C6H4OCH2CN(2, 3, or 4)
CH3


23.
NHCH2C6H4OCH2CONH2(2, 3, or 4)
H


24.
NHCH2C6H4OCH2CONH2(2, 3, or 4)
CH3


25.
NHCH2C6H3(CN)2(3, 5)
H


26.
NHCH2C6H3(CN)2(3, 5)
CH3


27.
NHCH2C6H3(CONH2)2(3, 5)
H


28.
NHCH2C6H3(CONH2)2(3, 5)
CH3


29.
NHCH2C6H4—NO2(2, 3, or 4)
H


30.
NHCH2C6H4—NO2(2, 3, or 4)
CH3


31.
NHCH2C6H4—CF3(2, 3, or 4)
H


32.
NHCH2C6H4—CF3(2, 3, or 4)
CH3


33.
NHCH2C6H4—CH3(2, 3, or 4)
H


34.
NHCH2C6H4—CH3(2, 3, or 4)
CH3


35.
NHCH2C6H4—NHSO2CH3(2, 3, or 4)
H


36.
NHCH2C6H4—NHSO2CH3(2, 3, or 4)
CH3


37.
NHCH2C6H4C6H4CN(2, 3, or 4)
H


38.
NHCH2C6H4C6H4CN(2, 3, or 4)
CH3


39.
NHCH2C6H4C6H4CONH2(2, 3, or 4)
H


40.
NHCH2C6H4C6H4CONH2(2, 3, or 4)
CH3


41.
NHCH2C6H4C6H4CO2H(2, 3, or 4)
H


42.
NHCH2C6H4C6H4CO2H(2, 3, or 4)
CH3
















TABLE VIIId




















1.
NHCH2C6H5
H












2.
NHCH2C6H5
CH3


3.
NHCH2C6H4C6H5
H


4.
NHCH2C6H4C6H5
CH3


5.
NHCH2CH2C6H5
H


6.
NHCH2CH2C6H5
CH3


7.
NHCH2C6H4—Cl(2, 3, or 4)
H


8.
NHCH2C6H4—Cl(2, 3, or 4)
CH3


9.
NHCH2C6H4—OCH3(2, 3, or 4)
H


10.
NHCH2C6H4—OCH3(2, 3, or 4)
CH3


11.
NHCH2C6H4—F(2, 3, or 4)
H


12.
NHCH2C6H4—F(2, 3, or 4)
CH3


13.
NHCH2C6H4CN(2, 3, or 4)
H


14.
NHCH2C6H4CN(2, 3, or 4)
CH3


15.
NHCH2C6H4CONH2(2, 3, or 4)
H


16.
NHCH2C6H4CONH2(2, 3, or 4)
CH3


17.
NHCH2C6H4CH2CN(2, 3, or 4)
H


18.
NHCH2C6H4CH2CN(2, 3, or 4)
CH3


19.
NHCH2C6H4CH2CONH2(2, 3, or 4)
H


20.
NHCH2C6H4CH2CONH2(2, 3, or 4)
CH3


21.
NHCH2C6H4OCH2CN(2, 3, or 4)
H


22.
NHCH2C6H4OCH2CN(2, 3, or 4)
CH3


23.
NHCH2C6H4OCH2CONH2(2, 3, or 4)
H


24.
NHCH2C6H4OCH2CONH2(2, 3, or 4)
CH3


25.
NHCH2C6H3(CN)2(3, 5)
H


26.
NHCH2C6H3(CN)2(3, 5)
CH3


27.
NHCH2C6H3(CONH2)2(3, 5)
H


28.
NHCH2C6H3(CONH2)2(3, 5)
CH3


29.
NHCH2C6H4—NO2(2, 3, or 4)
H


30.
NHCH2C6H4—NO2(2, 3, or 4)
CH3


31.
NHCH2C6H4—CF3(2, 3, or 4)
H


32.
NHCH2C6H4—CF3(2, 3, or 4)
CH3


33.
NHCH2C6H4—CH3(2, 3, or 4)
H


34.
NHCH2C6H4—CH3(2, 3, or 4)
CH3


35.
NHCH2C6H4—NHSO2CH3(2, 3, or 4)
H


36.
NHCH2C6H4—NHSO2CH3(2, 3, or 4)
CH3


37.
NHCH2C6H4C6H4CN(2, 3, or 4)
H


38.
NHCH2C6H4C6H4CN(2, 3, or 4)
CH3


39.
NHCH2C6H4C6H4CONH2(2, 3, or 4)
H


40.
NHCH2C6H4C6H4CONH2(2, 3, or 4)
CH3


41.
NHCH2C6H4C6H4CO2H(2, 3, or 4)
H


42.
NHCH2C6H4C6H4CO2H(2, 3, or 4)
CH3
















TABLE IXa













 









Ex #
X
R1












1.
O(CH2CH2O)2CH2CH2OH
H


2.
O(CH2CH2O)2CH2CH2OH
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
H


6.
O(CH2CH2O)3CH2CH2OH
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
H


10.
O(CH2CH2O)4CH2CH2OH
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
H


14.
O(CH2CH2O)5CH2CH2OH
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
H


18.
O(CH2CH2O)7CH2CH2OH
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
H


22.
O(CH2CH2O)9CH2CH2OH
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3
















TABLE IXb













 









Ex #
X
R1












1.
O(CH2CH2O)2CH2CH2OH
H


2.
O(CH2CH2O)2CH2CH2OH
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
H


6.
O(CH2CH2O)3CH2CH2OH
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
H


10.
O(CH2CH2O)4CH2CH2OH
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
H


14.
O(CH2CH2O)5CH2CH2OH
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
H


18.
O(CH2CH2O)7CH2CH2OH
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
H


22.
O(CH2CH2O)9CH2CH2OH
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3
















TABLE Xa













 










Number
X
Q
R1













1.
O(CH2CH2O)2CH2CH2OH
CH3
H


2.
O(CH2CH2O)2CH2CH2OH
CH3
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
CH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
CH3
H


6.
O(CH2CH2O)3CH2CH2OH
CH3
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
CH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
CH3
H


10.
O(CH2CH2O)4CH2CH2OH
CH3
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
CH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
CH3
H


14.
O(CH2CH2O)5CH2CH2OH
CH3
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
CH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
CH3
H


18.
O(CH2CH2O)7CH2CH2OH
CH3
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
CH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
CH3
H


22.
O(CH2CH2O)9CH2CH2OH
CH3
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
CH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3
CH3


25.
O(CH2CH2O)2CH2CH2OH
CH2C≡CH
H


26.
O(CH2CH2O)2CH2CH2OH
CH2C≡CH
CH3


27.
O(CH2CH2O)2CH2CH2OCH3
CH2C≡CH
H


28.
O(CH2CH2O)2CH2CH2OCH3
CH2C≡CH
CH3


29.
O(CH2CH2O)3CH2CH2OH
CH2C≡CH
H


30.
O(CH2CH2O)3CH2CH2OH
CH2C≡CH
CH3


31.
O(CH2CH2O)3CH2CH2OCH3
CH2C≡CH
H


32.
O(CH2CH2O)3CH2CH2OCH3
CH2C≡CH
CH3


33.
O(CH2CH2O)4CH2CH2OH
CH2C≡CH
H


34.
O(CH2CH2O)4CH2CH2OH
CH2C≡CH
CH3


35.
O(CH2CH2O)4CH2CH2OCH3
CH2C≡CH
H


36.
O(CH2CH2O)4CH2CH2OCH3
CH2C≡CH
CH3


37.
O(CH2CH2O)5CH2CH2OH
CH2C≡CH
H


38.
O(CH2CH2O)5CH2CH2OH
CH2C≡CH
CH3


39.
O(CH2CH2O)5CH2CH2OCH3
CH2C≡CH
H


40.
O(CH2CH2O)5CH2CH2OCH3
CH2C≡CH
CH3


41.
O(CH2CH2O)7CH2CH2OH
CH2C≡CH
H


42.
O(CH2CH2O)7CH2CH2OH
CH2C≡CH
CH3


43.
O(CH2CH2O)7CH2CH2OCH3
CH2C≡CH
H


44.
O(CH2CH2O)7CH2CH2OCH3
CH2C≡CH
CH3


45.
O(CH2CH2O)9CH2CH2OH
CH2C≡CH
H


46.
O(CH2CH2O)9CH2CH2OH
CH2C≡CH
CH3


47.
O(CH2CH2O)9CH2CH2OCH3
CH2C≡CH
H


48.
O(CH2CH2O)9CH2CH2OCH3
CH2C≡CH
CH3
















TABLE Xb













 










Number
X
Q
R1













1.
O(CH2CH2O)2CH2CH2OH
CH3
H


2.
O(CH2CH2O)2CH2CH2OH
CH3
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
CH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
CH3
H


6.
O(CH2CH2O)3CH2CH2OH
CH3
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
CH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
CH3
H


10.
O(CH2CH2O)4CH2CH2OH
CH3
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
CH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
CH3
H


14.
O(CH2CH2O)5CH2CH2OH
CH3
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
CH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
CH3
H


18.
O(CH2CH2O)7CH2CH2OH
CH3
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
CH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
CH3
H


22.
O(CH2CH2O)9CH2CH2OH
CH3
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
CH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3
CH3


25.
O(CH2CH2O)2CH2CH2OH
CH2C≡CH
H


26.
O(CH2CH2O)2CH2CH2OH
CH2C≡CH
CH3


27.
O(CH2CH2O)2CH2CH2OCH3
CH2C≡CH
H


28.
O(CH2CH2O)2CH2CH2OCH3
CH2C≡CH
CH3


29.
O(CH2CH2O)3CH2CH2OH
CH2C≡CH
H


30.
O(CH2CH2O)3CH2CH2OH
CH2C≡CH
CH3


31.
O(CH2CH2O)3CH2CH2OCH3
CH2C≡CH
H


32.
O(CH2CH2O)3CH2CH2OCH3
CH2C≡CH
CH3


33.
O(CH2CH2O)4CH2CH2OH
CH2C≡CH
H


34.
O(CH2CH2O)4CH2CH2OH
CH2C≡CH
CH3


35.
O(CH2CH2O)4CH2CH2OCH3
CH2C≡CH
H


36.
O(CH2CH2O)4CH2CH2OCH3
CH2C≡CH
CH3


37.
O(CH2CH2O)5CH2CH2OH
CH2C≡CH
H


38.
O(CH2CH2O)5CH2CH2OH
CH2C≡CH
CH3


39.
O(CH2CH2O)5CH2CH2OCH3
CH2C≡CH
H


40.
O(CH2CH2O)5CH2CH2OCH3
CH2C≡CH
CH3


41.
O(CH2CH2O)7CH2CH2OH
CH2C≡CH
H


42.
O(CH2CH2O)7CH2CH2OH
CH2C≡CH
CH3


43.
O(CH2CH2O)7CH2CH2OCH3
CH2C≡CH
H


44.
O(CH2CH2O)7CH2CH2OCH3
CH2C≡CH
CH3


45.
O(CH2CH2O)9CH2CH2OH
CH2C≡CH
H


46.
O(CH2CH2O)9CH2CH2OH
CH2C≡CH
CH3


47.
O(CH2CH2O)9CH2CH2OCH3
CH2C≡CH
H


48.
O(CH2CH2O)9CH2CH2OCH3
CH2C≡CH
CH3









Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein.

## Claims

1. A compound selected from Table A, or a stereoisomer or pharmaceutically acceptable salt thereof







TABLE A













 
















NMR



Ex #
X
Y
Z
(Solvent)
Scheme















1
OCH2C6H5
H2
H
(CDCl3)
4, 9






CH3: 0.97(d)







C≡CH: 2.25(m)







PhCH: 2.35(m)







NCH3: 2.43(s)







PhCH: 2.96(m)







NCH: 3.01(m)







NCH2: 3.44(m)







PhCH2O: 5.04(s)







aromatic H's 6.89-7.44



2
OCH2C6H4—
H2
H
(CDCl3)
4



CO2CH3 (3)


CH3: 0.98(d)







C≡CH: 2.27(m)







PhCH: 2.36(m)







NCH3: 2.44(s)







PhCH: 2.93(m)







NCH: 3.00(m)







NCH2: 3.45(q)







OCH3: 3.93(s)







PhCH2O: 5.08(s)







aromatic H's 6.89-8.11



3
OCH2C6H4—
H2
H
(CDCl3)
4



CONH2 (4)


CH3: 1.00(d)







C≡CH: 2.17(m)







PhCH: 2.30(m)







NCH3: 2.47(s)







PhCH: 3.00(m)







NCH: 3.00(m)







NCH2: 3.48(m)







OCH3: 3.92(s)







PhCH2O: 5.11(s)







aromatic H's 6.89, 7.10,







7.52, 7.84 d's



4
OCH2C6H4—
H2
H
(CD3OD)
4



CONH2 (3)


CH3: 0.98(d)







PhCH: 2.34(m)







NCH3: 2.41(s)







C≡CH: 2.70(m)







PhCH: 3.00(m)







NCH: 3.00(m)







NCH2: 3.45(m)







PhCH2O: 5.12(s)







aromatic H's 6.93-7.97



5
OCH2CH═CH—
H2
H
(CDCl3)
3



CO2CH2CH3


CH3: 0.96(d)







ester-CH3: 1.30(t)







C≡CH: 2.25(m)







PhCH: 2.35(m)







NCH3: 2.42(s)







PhCH: 2.95(m)







NCH: 2.99(m)







NCH2: 3.43(q)







OCH2: 4.22(q)







OCH2vinyl: 4.68(m)







CH═: 6.19(dt)







CH═: 7.06(dt)







C6H4: 6.83, 7.09(dd)



6
OCH2C6H5
O
OCH3
(CDCl3)
1






C≡CH: 2.17(m)







PhCH2: 2.93(dq)







NCH2: 3.39(dq)







OCH3: 3.67(s)







NCH: 3.70(m)







PhCH2O: 5.03(s)







aromatic H's 6.89-7.40



7
OCH2C6H4—
H2
H
(CD3OD)
4



OCH2CONH2


CH3: 0.96(d)




(3)


PhCH: 2.35(m)







NCH3: 2.42(s)







C≡CH: 2.70(m)







PhCH: 2.99(m)







NCH2: 3.46(m)







PhCH2CO: 3.54(s)







PhCH2O: 5.05(s)







aromatic H's 6.90-7.41



8
OCH2C6H4—
H2
H
(CD3OD)
4



CH2CONH2 (3)


CH3: 0.96(d)







PhCH: 2.33(m)







NCH3: 2.40(s)







C≡CH: 2.70(m)







PhCH: 3.00(m)







NCH2: 3.48(m)







OCH2CO: 4.50(s)







PhCH2O: 5.04(s)







aromatic H's 6.90-7.33



9
H
H2
OH
(CDCl3)
1






C≡CH: 2.28(m)







NCH3: 2.42(s)







NCH, PhCH: 3.09(m)







NCH2, 3.38(m)







CH2O: 3.43(d)







aromatic H's 7.15-7.30



10
OCH2C6H5
H2
OH
(CDCl3)
1






C≡CH: 2.30(m)







PhCH: 2.35(t)







NCH3: 2.45(s)







PhCH: 3.01(m)







NCH: 3.04(m)







NCH2, 3.40(m)







CH2O: 3.47(d)







PhCH2O: 5.04(s)







aromatic H's 6.89-7.44



11
OCH2C6H5
O
OCH3
(CDCl3)
1






C≡CH: 2.27(m)







NCH3: 2.46(s)







PhCH2: 2.97(d)







NCH2: 3.50(dq)







OCH3: 3.57(s)







NCH: 3.58(m)







PhCH2O: 5.03(s)







aromatic H's 6.88-7.41



13
OCH2C6H4CH3
H2
H
(CDCl3)
4,9



(3)


CH3: 0.97(d)







C≡CH: 2.24(m)







PhCH: 2.36(m)







PhCH3: 2.37(s)







NCH3: 2.42(s)







PhCH: 2.97(m)







NCH: 3.05(m)







NCH2: 3.43(q)







PhCH2O: 5.00(s)







aromatic H's: 6.89-7.29



14
OCH2C6H4CF3
H2
H
(CDCl3)
4, 9



(3)


CH3: 0.99(d)







C≡CH: 2.27(m)







PhCH: 2.38(m)







NCH3: 2.45(s)







PhCH: 2.97(m)







NCH: 3.00(m)







NCH2: 3.47(q)







PhCH2O: 5.09(s)







aromatic H's: 6.89-7.63



15
OCH2C6H4CH3
H2
H
(CDCl3)
4, 9



(4)


CH3: 0.96(d)







C≡CH: 2.24(m)







PhCH: 2.35(m)







PhCH3: 2.36(s)







NCH3: 2.42(s)







PhCH: 2.95(m)







NCH: 2.97(m)







NCH2: 3.42(q)







PhCH2O: 4.99(s)







aromatic H's: 6.88-7.32



16
OCH2C6H4CN
H2 
H
(CDCl3)
4, 9



(3)


CH3: 0.97(d)







C≡CH: 2.26(m)







PhCH: 2.38(m)







NCH3: 2.43(s)







PhCH: 2.97(m)







NCH: 2.99(m)







NCH2: 3.44(q)







PhCH2O: 5.07(s)







aromatic H's: 6.87-7.65



17
NHCH2C6H4CN
H2
H
(CDCl3)
5



(4)


CH3: 0.97(d)







C≡CH: 2.22(m)







PhCH: 2.27(m)







NCH3: 2.39(s)







PhCH: 2.86(m)







NCH: 2.91(m)







NCH2: 3.40(q)







PhCH2N: 4.39(s)







aromatic H's: 6.50(d),







6.97(d), 7.47(d), 7.60(d)



18
NHCH2C6H4OH
H2
H
(CDCl3)
5



(4)


CH3: 0.96(d)







C≡CH: 2.24(m)







PhCH: 2.27(m)







NCH3: 2.42(s)







PhCH: 2.86(m)







NCH: 2.91(m)







NCH2: 3.43(q)







PhCH2N: 4.21(s)







aromatic H's: 6.57(d),







6.80(d), 6.97(d), 7.23(d)



19
NHCH2C6H4OH
H2
H
(CDCl3)
5



(3)


CH3: 0.95(d)







CCH: 2.23(m)







PhCH: 2.28(m)







NCH3: 2.41(s)







PhCH: 2.89(m)







NCH: 2.92(m)







NCH2: 3.42(q)







PhCH2N: 4.26(s)







aromatic H's: 6.53-7.20.

2. A compound selected from Tables I, IIa, IIb, Ma, IIIb, IVa, IVb, IVc, IVd, V, VIIIa, VIIIb, VIIIc, VIIId, IXa, and IXb, or a stereoisomer or pharmaceutically acceptable salt thereof







TABLE I













 











Ex. # 
X
X1
R
R1














1
H
H
CH3
H


2
H
H
H
H


3
H
H
CH3
CH3


4
H
H
H
CH3


5
OH
H
CH3
H


6
OH
H
H
H


7
OH
H
CH3
CH3


8
OH
H
H
CH3


9
OCH3
H
CH3
H


10
OCH3
H
H
H


11
OCH3
H
CH3 
CH3


12
OCH3
H
H
CH3


13
OCH2C6H5
H
CH3
H


14
OCH2C6H5
H
H
H


15
OCH2C6H5
H
CH3 
CH3


16
OCH2C6H5
H
H
CH3


17
OCH2CH2C6H5
H
CH3
H


18
OCH2CH2C6H5
H
H
H


19
OCH2CH2C6H5
H
CH3 
CH3


20
OCH2CH2C6H5
H
H
CH3


21
OCH2CH═CH2
H
CH3
H


22
OCH2CH═CH2
H
H
H


23
OCH2CH═CH2
H
CH3 
CH3


24
OCH2CH═CH2
H
H
CH3


25
OCH2CONH2
H
CH3
H


26
OCH2CONH2
H
H
H


27
OCH2CONH2
H
CH3 
CH3


28
OCH2CONH2
H
H
CH3


29
Cl
H
CH3
H


30
Cl
H
H
H


31
Cl
H
CH3 
CH3


32
Cl
H
H
CH3


33
NO2
H
CH3
H


34
NO2
H
H
H


35
NO2
H
CH3 
CH3


36
NO2
H
H
CH3


41
NHSO2CH3
H
CH3
H


42
NHSO2CH3
H
H
H


43
NHSO2CH3
H
CH3
CH3


44
NHSO2CH3
H
H
CH3


45
OH
CH2N(CH3)2
CH3
H


46
OH
CH2N(CH3)2
H
H


47
OH
CH2N(CH3)2
CH3
CH3


48
OH
CH2N(CH3)2
H
CH3


49
OH
CH2N+(CH3)3Cl−
CH3
H


50
OH
CH2N+(CH3)3Cl−
H
H


51
OH
CH2N+(CH3)3Cl−
CH3
CH3


52
OH
CH2N+(CH3)3Cl−
H
CH3


53
OCH3
CH2N(CH3)2
CH3
H


54
OCH3
CH2N(CH3)2
H
H


55
OCH3
CH2N(CH3)2
CH3
CH3


56
OCH3
CH2N(CH3)2
H
CH3


57
OCH3
CH2N+(CH3)3Cl−
CH3
H


58
OCH3
CH2N+(CH3)3Cl−
H
H


59
OCH3
CH2N+(CH3)3Cl−
CH3
CH3


60
OCH3
CH2N+(CH3)3Cl−
H
CH3
















TABLE II













 










Ex. #
X
X1
R1













1
H
H
CO2CH2CH3


2
H
H
CO2H


3
OH
H
CO2CH2CH3


4
OH
H
CO2H


5
OCH3
H
CO2CH2CH3


6
OCH3
H
CO2H


7
OCH2CH═CH2
H
CO2CH2CH3


8
OCH2CH═CH2
H
CO2H


9
OCH2C6H5
H
CO2CH2CH3


10
OCH2C6H5
H
CO2H


11
OCH2CH2C6H5
H
CO2CH2CH3


12
OCH2CH2C6H5
H
CO2H


13
OCH2CONH2
H
CO2CH2CH3


14
OCH2CONH2
H
CO2H


15
Cl
H
CO2CH2CH3


16
Cl
H
CO2H


17
NO2
H
CO2CH2CH3


18
NO2
H
CO2H


21
NHSO2CH3
H
CO2CH2CH3


22
NHSO2CH3
H
CO2H


23
OH
CH2N(CH3)2
CO2CH2CH3


24
OH
CH2N(CH3)2
CO2H


25
OCH3
CH2N(CH3)2
CO2CH2CH3


26
OCH3
CH2N(CH3)2
CO2H


27
OCH2C6H5
CH2N(CH3)2
CO2CH2CH3


28
OCH2C6H5
CH2N(CH3)2
CO2H


29
OH
CH2N+(CH3)3Cl−
CO2CH2CH3


30
OH
CH2N+(CH3)3Cl−
CO2H


31
OCH3
CH2N+(CH3)3Cl−
CO2CH2CH3


32
OCH3
CH2N+(CH3)3Cl−
CO2H


33
OCH2C6H5
CH2N+(CH3)3Cl−
CO2CH2CH3


34
OCH2C6H5
CH2N+(CH3)3Cl−
CO2H


35
H
H
CH2CO2CH2CH3


36
H
H
CH2CO2H


37
OH
H
CH2CO2CH2CH3


38
OH
H
CH2CO2H


39
OCH3
H
CH2CO2CH2CH3


40
OCH3
H
CH2CO2H


41
OCH2CH═CH2
H
CH2CO2CH2CH3


42
OCH2CH═CH2
H
CH2CO2H


43
OCH2C6H5
H
CH2CO2CH2CH3


44
OCH2C6H5
H
CH2CO2H


45
OCH2CH2C6H5
H
CH2CO2CH2CH3


46
OCH2CH2C6H5
H
CH2CO2H


47
OCH2CONH2
H
CH2CO2CH2CH3


48
OCH2CONH2
H
CH2CO2H


49
Cl
H
CH2CO2CH2CH3


50
Cl
H
CH2CO2H


51
NO2
H
CH2CO2CH2CH3


52
NO2
H
CH2CO2H


55
NHSO2CH3
H
CH2CO2CH2CH3


56
NHSO2CH3
H
CH2CO2H


57
OH
CH2N(CH3)2
CH2CO2CH2CH3


58
OH
CH2N(CH3)2
CH2CO2H


59
OCH3
CH2N(CH3)2
CH2CO2CH2CH3


60
OCH3
CH2N(CH3)2
CH2CO2H


61
OCH2C6H5
CH2N(CH3)2
CH2CO2CH2CH3


62
OCH2C6H5
CH2N(CH3)2
CH2CO2H


63
OH
CH2N+(CH3)3Cl−
CH2CO2CH2CH3


64
OH
CH2N+(CH3)3Cl−
CH2CO2H


65
OCH3
CH2N+(CH3)3Cl−
CH2CO2CH2CH3


66
OCH3
CH2N+(CH3)3Cl−
CH2CO2H


67
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CO2CH2CH3


68
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CO2H


69
H
H
CH2CH2CO2CH2CH3


70
H
H
CH2CH2CO2H


71
OH
H
CH2CH2CO2CH2CH3


72
OH
H
CH2CH2CO2H


73
OCH3
H
CH2CH2CO2CH2CH3


74
OCH3
H
CH2CH2CO2H


75
OCH2CH═CH2
H
CH2CH2CO2CH2CH3


76
OCH2CH═CH2
H
CH2CH2CO2H


77
OCH2C6H5
H
CH2CH2CO2CH2CH3


78
OCH2C6H5
H
CH2CH2CO2H


79
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3


80
OCH2CH2C6H5
H
CH2CH2CO2H


81
OCH2CONH2
H
CH2CH2CO2CH2CH3


82
OCH2CONH2
H
CH2CH2CO2H


83
Cl
H
CH2CH2CO2CH2CH3


84
Cl
H
CH2CH2CO2H


85
NO2
H
CH2CH2CO2CH2CH3


86
NO2
H
CH2CH2CO2H


89
NHSO2CH3
H
CH2CH2CO2CH2CH3


90
NHSO2CH3
H
CH2CH2CO2H


91
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3


92
OH
CH2N(CH3)2
CH2CH2CO2H


93
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3


94
OCH3
CH2N(CH3)2
CH2CH2CO2H


95
OCH2C6H5
CH2N(CH3)2
CH2CH2CO2CH2CH3


96
OCH2C6H5
CH2N(CH3)2
CH2CH2CO2H


97
OH
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3


98
OH
CH2N+(CH3)3Cl−
CH2CH2CO2H


99
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3


100
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2H


101
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3


102
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH2CO2H


103
H
H
CH2CH═CHCO2CH2CH3


104
H
H
CH2CH═CHCO2H


105
OH
H
CH2CH═CHCO2CH2CH3


106
OH
H
CH2CH═CHCO2H


107
OCH3
H
CH2CH═CHCO2CH2CH3


108
OCH3
H
CH2CH═CHCO2H


109
OCH2CH═CH2
H
CH2CH═CHCO2CH2CH3


110
OCH2CH═CH2
H
CH2CH═CHCO2H


111
OCH2C6H5
H
CH2CH═CHCO2CH2CH3


112
OCH2C6H5
H
CH2CH═CHCO2H


113
OCH2CH2C6H5
H
CH2CH═CHCO2CH2CH3


114
OCH2CH2C6H5
H
CH2CH═CHCO2H


115
OCH2CONH2
H
CH2CH═CHCO2CH2CH3


116
OCH2CONH2
H
CH2CH═CHCO2H


117
Cl
H
CH2CH═CHCO2CH2CH3


118
Cl
H
CH2CH═CHCO2H


119
NO2
H
CH2CH═CHCO2CH2CH3


120
NO2
H
CH2CH═CHCO2H


123
NHSO2CH3
H
CH2CH═CHCO2CH2CH3


124
NHSO2CH3
H
CH2CH═CHCO2H


125
OH
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


126
OH
CH2N(CH3)2
CH2CH═CHCO2H


127
OCH3
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


128
OCH3
CH2N(CH3)2
CH2CH═CHCO2H


129
OCH2C6H5
CH2N(CH3)2
CH2CH═CHCO2CH2CH3


130
OCH2C6H5
CH2N(CH3)2
CH2CH═CHCO2H


131
OH
CH2N+(CH3)3Cl−
CH2CH═CHCO2CH2CH3


132
OH
CH2N+(CH3)3Cl−
CH2CH═CHCO2H


133
OCH3
CH2N+(CH3)3Cl−
CH2CH═CHCO2CH2CH3


134
OCH3
CH2N+(CH3)3Cl−
CH2CH═CHCO2H


135
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH═CHCO2CH2CH3


136
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH═CHCO2H


137
H
H
CH2CH2PO(OCH2CH3)2


138
H
H
CH2CH2PO(OH)2


139
OH
H
CH2CH2PO(OCH2CH3)2


140
OH
H
CH2CH2PO(OH)2


141
OCH3
H
CH2CH2PO(OCH2CH3)2


142
OCH3
H
CH2CH2PO(OH)2


143
OCH2CH═CH2
H
CH2CH2PO(OCH2CH3)2


144
OCH2CH═CH2
H
CH2CH2PO(OH)2


145
OCH2C6H5
H
CH2CH2PO(OCH2CH3)2


146
OCH2C6H5
H
CH2CH2PO(OH)2


147
OCH2CH2C6H5
H
CH2CH2PO(OCH2CH3)2


148
OCH2CH2C6H5
H
CH2CH2PO(OH)2


149
OCH2CONH2
H
CH2CH2PO(OCH2CH3)2


150
OCH2CONH2
H
CH2CH2PO(OH)2


151
Cl
H
CH2CH2PO(OCH2CH3)2


152
Cl
H
CH2CH2PO(OH)2


153
NO2
H
CH2CH2PO(OCH2CH3)2


154
NO2
H
CH2CH2PO(OH)2


157
NHSO2CH3
H
CH2CH2PO(OCH2CH3)2


158
NHSO2CH3
H
CH2CH2PO(OH)2


159
OH
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


160
OH
CH2N(CH3)2
CH2CH2PO(OH)2


161
OCH3
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


162
OCH3
CH2N(CH3)2
CH2CH2PO(OH)2


163
OCH2C6H5
CH2N(CH3)2
CH2CH2PO(OCH2CH3)2


164
OCH2C6H5
CH2N(CH3)2
CH2CH2PO(OH)2


165
OH
CH2N+(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


166
OH
CH2N+(CH3)3Cl−
CH2CH2PO(OH)2


167
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


168
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO(OH)2


169
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH2PO(OCH2CH3)2


170
OCH2C6H5
CH2N+(CH3)3Cl−
CH2CH2PO(OH)2
















TABLE IIIa













 











Ex. #
X
Xl
Z1
R1














1
H
H
CH2CO2CH2CH3
H


2
H
H
CH2CO2H
H


3
H
H
CH2CO2CH2CH3
CH3


4
H
H
CH2CO2H
CH3


5
OH
H
CH2CO2CH2CH3
H


6
OH
H
CH2CO2H
H


7
OH
H
CH2CO2CH2CH3
CH3


8
OH
H
CH2CO2H
CH3


9
OCH3
H
CH2CO2CH2CH3
H


10
OCH3
H
CH2CO2H
H


11
OCH3
H
CH2CO2CH2CH3
CH3


12
OCH3
H
CH2CO2H
CH3


13
OCH2C6H5
H
CH2CO2CH2CH3
H


14
OCH2C6H5
H
CH2CO2H
H


15
OCH2C6H5
H
CH2CO2CH2CH3
CH3


16
OCH2C6H5
H
CH2CO2H
CH3


17
OCH2CH2C6H5
H
CH2CO2CH2CH3
H


18
OCH2CH2C6H5
H
CH2CO2H
H


19
OCH2CH2C6H5
H
CH2CO2CH2CH3
CH3


20
OCH2CH2C6H5
H
CH2CO2H
CH3


21
OCH2CH═CH2
H
CH2CO2CH2CH3
H


22
OCH2CH═CH2
H
CH2CO2H
H


23
OCH2CH═CH2
H
CH2CO2CH2CH3
CH3


24
OCH2CH═CH2
H
CH2CO2H
CH3


25
OCH2CONH2
H
CH2CO2CH2CH3
H


26
OCH2CONH2
H
CH2CO2H
H


27
OCH2CONH2
H
CH2CO2CH2CH3
CH3


28
OCH2CONH2
H
CH2CO2H
CH3


29
Cl
H
CH2CO2CH2CH3
H


30
Cl
H
CH2CO2H
H


31
Cl
H
CH2CO2CH2CH3
CH3


32
Cl
H
CH2CO2H
CH3


33
NO2
H
CH2CO2CH2CH3
H


34
NO2
H
CH2CO2H
H


35
NO2
H
CH2CO2CH2CH3
CH3


36
NO2
H
CH2CO2H
CH3


41
NHSO2CH3
H
CH2CO2CH2CH3
H


42
NHSO2CH3
H
CH2CO2H
H


43
NHSO2CH3
H
CH2CO2CH2CH3
CH3


44
NHSO2CH3
H
CH2CO2H
CH3


45
OH
CH2N(CH3)2
CH2CO2CH2CH3
H


46
OH
CH2N(CH3)2
CH2CO2H
H


47
OH
CH2N(CH3)2
CH2CO2CH2CH3
CH3


48
OH
CH2N(CH3)2
CH2CO2H
CH3


49
OH
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
H


50
OH
CH2N+(CH3)3Cl−
CH2CO2H
H


51
OH
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
CH3


52
OH
CH2N+(CH3)3Cl−
CH2CO2H
CH3


53
OCH3
CH2N(CH3)2
CH2CO2CH2CH3
H


54
OCH3
CH2N(CH3)2
CH2CO2H
H


55
OCH3
CH2N(CH3)2
CH2CO2CH2CH3
CH3


56
OCH3
CH2N(CH3)2
CH2CO2H
CH3


57
OCH3
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
H


58
OCH3
CH2N+(CH3)3Cl−
CH2CO2H
H


59
OCH3
CH2N+(CH3)3Cl−
CH2CO2CH2CH3
CH3


60
OCH3
CH2N+(CH3)3Cl−
CH2CO2H
CH3


61
H
H
CH2CH2CO2CH2CH3
H


62
H
H
CH2CH2CO2H
H


63
H
H
CH2CH2CO2CH2CH3
CH3


64
H
H
CH2CH2CO2H
CH3


65
OH
H
CH2CH2CO2CH2CH3
H


66
OH
H
CH2CH2CO2H
H


67
OH
H
CH2CH2CO2CH2CH3
CH3


68
OH
H
CH2CH2CO2H
CH3


69
OCH3
H
CH2CH2CO2CH2CH3
H


70
OCH3
H
CH2CH2CO2H
H


71
OCH3
H
CH2CH2CO2CH2CH3
CH3


72
OCH3
H
CH2CH2CO2H
CH3


73
OCH2C6H5
H
CH2CH2CO2CH2CH3
H


74
OCH2C6H5
H
CH2CH2CO2H
H


75
OCH2C6H5
H
CH2CH2CO2CH2CH3
CH3


76
OCH2C6H5
H
CH2CH2CO2H
CH3


77
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
H


78
OCH2CH2C6H5
H
CH2CH2CO2H
H


79
OCH2CH2C6H5
H
CH2CH2CO2CH2CH3
CH3


80
OCH2CH2C6H5
H
CH2CH2CO2H
CH3


81
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
H


82
OCH2CH═CH2
H
CH2CH2CO2H
H


83
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
CH3


84
OCH2CH═CH2
H
CH2CH2CO2H
CH3


85
OCH2CONH2
H
CH2CH2CO2CH2CH3
H


86
OCH2CONH2
H
CH2CH2CO2H
H


87
OCH2CONH2
H
CH2CH2CO2CH2CH3
CH3


88
OCH2CONH2
H
CH2CH2CO2H
CH3


89
Cl
H
CH2CH2CO2CH2CH3
H


90
Cl
H
CH2CH2CO2H
H


91
Cl
H
CH2CH2CO2CH2CH3
CH3


92
Cl
H
CH2CH2CO2H
CH3


93
NO2
H
CH2CH2CO2CH2CH3
H


94
NO2
H
CH2CH2CO2H
H


95
NO2
H
CH2CH2CO2CH2CH3
CH3


96
NO2
H
CH2CH2CO2H
CH3


101
NHSO2CH3
H
CH2CH2CO2CH2CH3
H


102
NHSO2CH3
H
CH2CH2CO2H
H


103
NHSO2CH3
H
CH2CH2CO2CH2CH3
CH3


104
NHSO2CH3
H
CH2CH2CO2H
CH3


105
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3
H


106
OH
CH2N(CH3)2
CH2CH2CO2H
H


107
OH
CH2N(CH3)2
CH2CH2CO2CH2CH3
CH3


108
OH
CH2N(CH3)2
CH2CH2CO2H
CH3


109
OH
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
H


110
OH
CH2N+(CH3)3Cl−
CH2CH2CO2H
H


111
OH
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
CH3


112
OH
CH2N+(CH3)3Cl−
CH2CH2CO2H
CH3


113
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3
H


114
OCH3
CH2N(CH3)2
CH2CH2CO2H
H


115
OCH3
CH2N(CH3)2
CH2CH2CO2CH2CH3
CH3


116
OCH3
CH2N(CH3)2
CH2CH2CO2H
CH3


117
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
H


1118 
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2H
H


119
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2CH2CH3
CH3


120
OCH3
CH2N+(CH3)3Cl−
CH2CH2CO2H
CH3


121
H
H
CH2CH2PO—
H





(OCH2CH3)2



122
H
H
CH2CH2PO—(OH)2
H


123
H
H
CH2CH2PO—
CH3





(OCH2CH3)2



124
H
H
CH2CH2PO—(OH)2
CH3


125
OH
H
CH2CH2PO—
H





(OCH2CH3)2



126
OH
H
CH2CH2PO—(OH)2
H


127
OH
H
CH2CH2PO—
CH3





(OCH2CH3)2



128
OH
H
CH2CH2PO—(OH)2
CH3


129
OCH3
H
CH2CH2PO—
H





(OCH2CH3)2



130
OCH3
H
CH2CH2PO—(OH)2
H


131
OCH3
H
CH2CH2PO—
CH3





(OCH2CH3)2



132
OCH3
H
CH2CH2PO—(OH)2
CH3


133
OCH2C6H5
H
CH2CH2PO—
H





(OCH2CH3)2



134
OCH2C6H5
H
CH2CH2PO—(OH)2
H


135
OCH2C6H5
H
CH2CH2PO—
CH3





(OCH2CH3)2



136
OCH2C6H5
H
CH2CH2PO—(OH)2
CH3


137
OCH2CH2C6H5
H
CH2CH2PO—
H





(OCH2CH3)2



138
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
H


139
OCH2CH2C6H5
H
CH2CH2PO—
CH3





(OCH2CH3)2



140
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
CH3


141
OCH2CH═CH2
H
CH2CH2PO—
H





(OCH2CH3)2



142
OCH2CH═CH2
H
CH2CH2PO—(OH)2
H


143
OCH2CH═CH2
H
CH2CH2PO—
CH3





(OCH2CH3)2



144
OCH2CH═CH2
H
CH2CH2PO—(OH)2
CH3


145
OCH2CONH2
H
CH2CH2PO—
H





(OCH2CH3)2



146
OCH2CONH2
H
CH2CH2PO—(OH)2
H


147
OCH2CONH2
H
CH2CH2PO—
CH3





(OCH2CH3)2



148
OCH2CONH2
H
CH2CH2PO—(OH)2
CH3


149
Cl
H
CH2CH2PO—
H





(OCH2CH3)2



150
Cl
H
CH2CH2PO—(OH)2
H


151
Cl
H
CH2CH2PO—
CH3





(OCH2CH3)2



152
Cl
H
CH2CH2PO—(OH)2
CH3


153
NO2
H
CH2CH2PO—
H





(OCH2CH3)2



154
NO2
H
CH2CH2PO—(OH)2
H


155
NO2
H
CH2CH2PO—
CH3





(OCH2CH3)2



156
NO2
H
CH2CH2PO—(OH)2
CH3


161
NHSO2CH3
H
CH2CH2PO—
H





(OCH2CH3)2



162
NHSO2CH3
H
CH2CH2PO—(OH)2
H


163
NHSO2CH3
H
CH2CH2PO—
CH3





(OCH2CH3)2



164
NHSO2CH3
H
CH2CH2PO—(OH)2
CH3


165
OH
CH2N(CH3)2
CH2CH2PO—
H





(OCH2CH3)2



166
OH
CH2N(CH3)2
CH2CH2PO—(OH)2
H


167
OH
CH2N(CH3)2
CH2CH2PO—
CH3





(OCH2CH3)2



168
OH
CH2N(CH3)2
CH2CH2PO—(OH)2
CH3


169
OH
CH2N+(CH3)3Cl−
CH2CH2PO—
H





(OCH2CH3)2



170
OH
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
H


171
OH
CH2N+(CH3)3Cl−
CH2CH2PO—
CH3





(OCH2CH3)2



172
OH
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
CH3


173
OCH3
CH2N(CH3)2
CH2CH2PO—
H





(OCH2CH3)2



174
OCH3
CH2N(CH3)2
CH2CH2PO—(OH)2
H


175
OCH3
CH2N(CH3)2
CH2CH2PO—
CH3





(OCH2CH3)2



176
OCH3
CH2N(CH3)2
CH2CH2PO—(OH)2
CH3


177
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—
H





(OCH2CH3)2



178
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
H


179
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—
CH3





(OCH2CH3)2



180
OCH3
CH2N+(CH3)3Cl−
CH2CH2PO—(OH)2
CH3


181
H
H
CH2CH2CONH—
H





CH(OH)CO2H



182
H
H
CH2CH2CONH—
CH3





CH(OH)CO2H



183
OH
H
CH2CH2CONH—
H





CH(OH)CO2H



184
OH
H
CH2CH2CONH—
CH3





CH(OH)CO2H



185
OCH3
H
CH2CH2CONH—
H





CH(OH)CO2H



186
OCH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



187
OCH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



188
OCH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



189
OCH2CH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



190
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



191
OCH2CH═CH2
H
CH2CH2CONH—
H





CH(OH)CO2H



192
OCH2CH═CH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



193
OCH2CONH2
H
CH2CH2CONH—
H





CH(OH)CO2H



194
OCH2CONH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



195
Cl
H
CH2CH2CONH—
H





CH(OH)CO2H



196
Cl
H
CH2CH2CONH—
CH3





CH(OH)CO2H



197
NO2
H
CH2CH2CONH—
H





CH(OH)CO2H



198
NO2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



201
NHSO2CH3
H
CH2CH2CONH—
H





CH(OH)CO2H



202
NHSO2CH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



203
OH
CH2N(CH3)2
CH2CH2CONH—
H





CH(OH)CO2H



204
OH
CH2N(CH3)2
CH2CH2CONH—
CH3





CH(OH)CO2H



205
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





CH(OH)CO2H



206
OH
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





CH(OH)CO2H



207
OCH3
CH2N(CH3)2
CH2CH2CONH—
H





CH(OH)CO2H



208
OCH3
CH2N(CH3)2
CH2CH2CONH—
CH3





CH(OH)CO2H



209
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
H





CH(OH)CO2H



210
OCH3
CH2N+(CH3)3Cl−
CH2CH2CONH—
CH3





CH(OH)CO2H



211
H
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



212
H
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



213
OH
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



214
OH
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



215
OCH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



216
OCH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



217
OCH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



218
OCH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



219
OCH2CH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



220
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



221
OCH2CH═CH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



222
OCH2CH═CH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



223
OCH2CONH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



224
OCH2CONH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



225
Cl
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



226
Cl
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



227
NO2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



228
NO2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



231
NHSO2CH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



232
NHSO2CH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



233
OH
CH2N(CH3)2
CH2CH2CONH—
H





C(CH3)2CH2SO3H



234
OH
CH2N(CH3)2
CH2CH2CONH—
CH3





C (CH3)2CH2SO3H



235
OH
CH2N+(CH3 )3C−
CH2CH2CONH—
H





C(CH3)2CH2SO3H



236
OH
CH2N+(CH3 )3Cl−
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



237
OCH3
CH2N(CH3)2
CH2CH2CONH—
H





C(CH3)2CH2SO3H



238
OCH3
CH2N(CH3)2
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



239
OCH3
CH2N+(CH3 )3Cl−
CH2CH2CONH—
H





C(CH3)2CH2SO3H



240
OCH3
CH2N+(CH3 )3Cl−
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H
















TABLE IIIb













 











Ex.






#
X
X1
Z1
R1














1
H
H
CH2CO2CH2CH3
H


2
H
H
CH2CO2H
H


3
H
H
CH2CO2CH2CH3
CH3


4
H
H
CH2CO2H
CH3


5
OH
H
CH2CO2CH2CH3
H


6
OH
H
CH2CO2H
H


7
OH
H
CH2CO2CH2CH3
CH3


8
OH
H
CH2CO2H
CH3


9
OCH3
H
CH2CO2CH2CH3
H


10
OCH3
H
CH2CO2H
H


11
OCH3
H
CH2CO2CH2CH3
CH3


12
OCH3
H
CH2CO2H
CH3


13
OCH2C6H5
H
CH2CO2CH2CH3
H


14
OCH2C6H5
H
CH2CO2H
H


15
OCH2C6H5
H
CH2CO2CH2CH3
CH3


16
OCH2C6H5
H
CH2CO2H
CH3


17
OCH2CH2C6H5
H
CH2CO2CH2CH3
H


18
OCH2CH2C6H5
H
CH2CO2H
H


19
OCH2CH2C6H5
H
CH2CO2CH2CH3
CH3


20
OCH2CH2C6H5
H
CH2CO2H
CH3


21
OCH2CH═CH2
H
CH2CO2CH2CH3
H


22
OCH2CH═CH2
H
CH2CO2H
H


23
OCH2CH═CH2
H
CH2CO2CH2CH3
CH3


24
OCH2CH═CH2
H
CH2CO2H
CH3


25
OCH2CONH2
H
CH2CO2CH2CH3
H


26
OCH2CONH2
H
CH2CO2H
H


27
OCH2CONH2
H
CH2CO2CH2CH3
CH3


28
OCH2CONH2
H
CH2CO2H
CH3


29
Cl
H
CH2CO2CH2CH3
H


30
Cl
H
CH2CO2H
H


31
Cl
H
CH2CO2CH2CH3
CH3


32
Cl
H
CH2CO2H
CH3


33
NO2
H
CH2CO2CH2CH3
H


34
NO2
H
CH2CO2H
H


35
NO2
H
CH2CO2CH2CH3
CH3


36
NO2
H
CH2CO2H
CH3


37
H
H
CH2CH2CO2CH2CH3
H


38
H
H
CH2CH2CO2H
H


39
H
H
CH2CH2CO2CH2CH3
CH3


40
H
H
CH2CH2CO2H
CH3


41
OH
H
CH2CH2CO2CH2CH3
H


42
OH
H
CH2CH2CO2H
H


43
OH
H
CH2CH2CO2CH2CH3
CH3


44
OH
H
CH2CH2CO2H
CH3


45
OCH3
H
CH2CH2CO2CH2CH3
H


46
OCH3
H
CH2CH2CO2H
H


47
OCH3
H
CH2CH2CO2CH2CH3
CH3


48
OCH3
H
CH2CH2CO2H
CH3


49
OCH2C6H5
H
CH2CH2CO2CH2CH3
H


50
OCH2C6H5
H
CH2CH2CO2H
H


51
OCH2C6H5
H
CH2CH2CO2CH2CH3
CH3


52
OCH2C6H5
H
CH2CH2CO2H
CH3


53
OCH2CH2C6H5 
H
CH2CH2CO2CH2CH3
H


54
OCH2CH2C6H5 
H
CH2CH2CO2H
H


55
OCH2CH2C6H5 
H
CH2CH2CO2CH2CH3
CH3


56
OCH2CH2C6H5 
H
CH2CH2CO2H
CH3


57
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
H


58
OCH2CH═CH2
H
CH2CH2CO2H
H


59
OCH2CH═CH2
H
CH2CH2CO2CH2CH3
CH3


60
OCH2CH═CH2
H
CH2CH2CO2H
CH3


61
OCH2CONH2
H
CH2CH2CO2CH2CH3
H


62
OCH2CONH2
H
CH2CH2CO2H
H


63
OCH2CONH2
H
CH2CH2CO2CH2CH3
CH3


64
OCH2CONH2
H
CH2CH2CO2H
CH3


65
Cl
H
CH2CH2CO2CH2CH3
H


66
Cl
H
CH2CH2CO2H
H


67
Cl
H
CH2CH2CO2CH2CH3
CH3


68
Cl
H
CH2CH2CO2H
CH3


69
NO2
H
CH2CH2CO2CH2CH3
H


70
NO2
H
CH2CH2CO2H
H


71
NO2
H
CH2CH2CO2CH2CH3
CH3


72
NO2
H
CH2CH2CO2H
CH3


73
H
H
CH2CH2PO—(OCH2CH3)2
H


74
H
H
CH2CH2PO—(OH)2
H


75
H
H
CH2CH2PO—(OCH2CH3)2
CH3


76
H
H
CH2CH2PO—(OH)2
CH3


77
OH
H
CH2CH2PO—(OCH2CH3)2
H


78
OH
H
CH2CH2PO—(OH)2
H


79
OH
H
CH2CH2PO—(OCH2CH3)2
CH3


80
OH
H
CH2CH2PO—(OH)2
CH3


81
OCH3
H
CH2CH2PO—(OCH2CH3)2
H


82
OCH3
H
CH2CH2PO—(OH)2
H


83
OCH3
H
CH2CH2PO—(OCH2CH3)2
CH3


84
OCH3
H
CH2CH2PO—(OH)2
CH3


85
OCH2C6H5
H
CH2CH2PO—(OCH2CH3)2
H


86
OCH2C6H5
H
CH2CH2PO—(OH)2
H


87
OCH2C6H5
H
CH2CH2PO—(OCH2CH3)2
CH3


88
OCH2C6H5
H
CH2CH2PO—(OH)2
CH3


89
OCH2CH2C6H5
H
CH2CH2PO—(OCH2CH3)2
H


90
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
H


91
OCH2CH2C6H5
H
CH2CH2PO—(OCH2CH3)2
CH3


92
OCH2CH2C6H5
H
CH2CH2PO—(OH)2
CH3


93
OCH2CH═CH2
H
CH2CH2PO—(OCH2CH3)2
H


94
OCH2CH═CH2
H
CH2CH2PO—(OH)2
H


95
OCH2CH═CH2
H
CH2CH2PO—(OCH2CH3)2
CH3


96
OCH2CH═CH2
H
CH2CH2PO—(OH)2
CH3


97
OCH2CONH2
H
CH2CH2PO—(OCH2CH3)2
H


98
OCH2CONH2
H
CH2CH2PO—(OH)2
H


99
OCH2CONH2
H
CH2CH2PO—(OCH2CH3)2
CH3


100
OCH2CONH2
H
CH2CH2PO—(OH)2
CH3


101
Cl
H
CH2CH2PO—(OCH2CH3)2
H


102
Cl
H
CH2CH2PO—(OH)2
H


103
Cl
H
CH2CH2PO—(OCH2CH3)2
CH3


104
Cl
H
CH2CH2PO—(OH)2
CH3


105
NO2
H
CH2CH2PO—(OCH2CH3)2
H


106
NO2
H
CH2CH2PO—(OH)2
H


107
NO2
H
CH2CH2PO—(OCH2CH3)2
CH3


108
NO2
H
CH2CH2PO—(OH)2
CH3


109
H
H
CH2CH2CONH—
H





CH(OH)CO2H



110
H
H
CH2CH2CONH—
CH3





CH(OH)CO2H



111
OH
H
CH2CH2CONH—
H





CH(OH)CO2H



112
OH
H
CH2CH2CONH—
CH3





CH(OH)CO2H



113
OCH3
H
CH2CH2CONH—
H





CH(OH)CO2H



114
OCH3
H
CH2CH2CONH—
CH3





CH(OH)CO2H



115
OCH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



116
OCH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



117
OCH2CH2C6H5
H
CH2CH2CONH—
H





CH(OH)CO2H



118
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





CH(OH)CO2H



119
OCH2CH═CH2
H
CH2CH2CONH—
H





CH(OH)CO2H



120
OCH2CH═CH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



121
OCH2CONH2
H
CH2CH2CONH—
H





CH(OH)CO2H



122
OCH2CONH2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



123
Cl
H
CH2CH2CONH—
H





CH(OH)CO2H



124
Cl
H
CH2CH2CONH—
CH3





CH(OH)CO2H



125
NO2
H
CH2CH2CONH—
H





CH(OH)CO2H



126
NO2
H
CH2CH2CONH—
CH3





CH(OH)CO2H



127
H
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



128
H
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



129
OH
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



130
OH
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



131
OCH3
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



132
OCH3
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



133
OCH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



134
OCH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



135
OCH2CH2C6H5
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



136
OCH2CH2C6H5
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



137
OCH2CH═CH2 
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



138
OCH2CH═CH2 
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



139
OCH2CONH2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



140
OCH2CONH2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



141
Cl
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



142
Cl
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H



143
NO2
H
CH2CH2CONH—
H





C(CH3)2CH2SO3H



144
NO2
H
CH2CH2CONH—
CH3





C(CH3)2CH2SO3H
















TABLE IVa













 










Ex.





#
X
Z
R1













1
OCH2CO2CH2CH3
H
H


2
OCH2CO2H
H
H


3
OCH2CO2CH2CH3
H
CH3


4
OCH2CO2H
H
CH3


5
OCH2CH2CO2CH2CH3
H
H


6
OCH2CH2CO2H
H
H


7
OCH2CH2CO2CH2CH3
H
CH3


8
OCH2CH2CO2H
H
CH3


9
OCH2CH2PO(OCH2CH3)2
H
H


10
OCH2CH2PO(OH)2
H
H


11
OCH2CH2PO(OCH2CH3)2
H
CH3


12
OCH2CH2PO(OH)2
H
CH3


13
OCH2CH═CHCO2CH2CH3
H
H


14
OCH2CH═CHCO2H
H
H


15
OCH2CH═CHCO2CH2CH3
H
CH3


16
OCH2CH═CHCO2H
H
CH3


17
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
H
H


18
OCH2C6H4CO2H (2, 3 or 4)
H
H


19
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
H
CH3


20
OCH2C6H4CO2H (2, 3 or 4)
H
CH3


21
OCH2C6H4CH2CO2CH2CH3 (2,
H
H



3 or 4)




22
OCH2C6H4CH2CO2H (2, 3 or 4)
H
H


23
OCH2C6H4CH2CO2CH2CH3 (2,
H
CH3



3 or 4)




24
OCH2C6H4CH2CO2H (2, 3 or 4)
H
CH3


25
OCH2CO2CH2CH3
OH
H


26
OCH2CO2H
OH
H


27
OCH2CO2CH2CH3
OH
CH3


28
OCH2CO2H
OH
CH3


29
OCH2CH2CO2CH2CH3
OH
H


30
OCH2CH2CO2H
OH
H


31
OCH2CH2CO2CH2CH3
OH
CH3


32
OCH2CH2CO2H
OH
CH3


33
OCH2CH2PO(OCH2CH3)2
OH
H


34
OCH2CH2PO(OH)2
OH
H


35
OCH2CH2PO(OCH2CH3)2
OH
CH3


36
OCH2CH2PO(OH)2
OH
CH3


37
OCH2CH═CHCO2CH2CH3
OH
H


38
OCH2CH═CHCO2H
OH
H


39
OCH2CH═CHCO2CH2CH3
OH
CH3


40
OCH2CH═CHCO2H
OH
CH3


41
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OH
H


42
OCH2C6H4CO2H (2, 3 or 4)
OH
H


43
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OH
CH3


44
OCH2C6H4CO2H (2, 3 or 4)
OH
CH3


45
OCH2C6H4CH2CO2CH2CH3 (2,
OH
H



3 or 4)




46
OCH2C6H4CH2CO2H (2, 3 or 4)
OH
H


47
OCH2C6H4CH2CO2CH2CH3 (2,
OH
CH3



3 or 4)




48
OCH2C6H4CH2CO2H (2, 3 or 4)
OH
CH3


49
OCH2CO2CH2CH3
OCH3
H


50
OCH2CO2H
OCH3
H


51
OCH2CO2CH2CH3
OCH3
CH3


52
OCH2CO2H
OCH3
CH3


53
OCH2CH2CO2CH2CH3
OCH3
H


54
OCH2CH2CO2H
OCH3
H


55
OCH2CH2CO2CH2CH3
OCH3
CH3


56
OCH2CH2CO2H
OCH3
CH3


57
OCH2CH2PO(OCH2CH3)2
OCH3
H


58
OCH2CH2PO(OH)2
OCH3
H


59
OCH2CH2PO(OCH2CH3)2
OCH3
CH3


60
OCH2CH2PO(OH)2
OCH3
CH3


61
OCH2CH═CHCO2CH2CH3
OCH3
H


62
OCH2CH═CHCO2H
OCH3
H


63
OCH2CH═CHCO2CH2CH3
OCH3
CH3


64
OCH2CH═CHCO2H
OCH3
CH3


65
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH3
H


66
OCH2C6H4CO2H (2, 3 or 4)
OCH3
H


67
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH3
CH3


68
OCH2C6H4CO2H (2, 3 or 4)
OCH3
CH3


69
OCH2C6H4CH2CO2CH2CH3 (2,
OCH3
H



3 or 4)




70
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH3
H


71
OCH2C6H4CH2CO2CH2CH3 (2,
OCH3
CH3



3 or 4)




72
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH3
CH3


73
OCH2CO2CH2CH3
OCH2CH═CH2
H


74
OCH2CO2H
OCH2CH═CH2
H


75
OCH2CO2CH2CH3
OCH2CH═CH2
CH3


76
OCH2CO2H
OCH2CH═CH2
CH3


77
OCH2CH2CO2CH2CH3
OCH2CH═CH2
H


78
OCH2CH2CO2H
OCH2CH═CH2
H


79
OCH2CH2CO2CH2CH3
OCH2CH═CH2
CH3


80
OCH2CH2CO2H
OCH2CH═CH2
CH3


81
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
H


82
OCH2CH2PO(OH)2
OCH2CH═CH2
H


83
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
CH3


84
OCH2CH2PO(OH)2
OCH2CH═CH2
CH3


85
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
H


86
OCH2CH═CHCO2H
OCH2CH═CH2
H


87
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
CH3


88
OCH2CH═CHCO2H
OCH2CH═CH2
CH3


89
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
H


90
OCH2C6H4CO2H (2, 3 or 4)
OCH2CH═CH2
H


91
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
CH3


92
OCH2C6H4CO2H (2, 3 or 4)
OCH2CH═CH2
CH3


93
OCH2C6H4CH2CO2CH2CH3 (2,
OCH2CH═CH2
H



3 or 4)




94
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH2CH═CH2
H


95
OCH2C6H4CH2CO2CH2CH3 (2,
OCH2CH═CH2
CH3



3 or 4)




96
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH2CH═CH2
CH3


97
OCH2CO2CH2CH3
OCH2C6CH5
H


98
OCH2CO2H
OCH2C6CH5
H


99
OCH2CO2CH2CH3
OCH2C6CH5
CH3


100
OCH2CO2H
OCH2C6CH5
CH3


101
OCH2CH2CO2CH2CH3
OCH2C6CH5
H


102
OCH2CH2CO2H
OCH2C6CH5
H


103
OCH2CH2CO2CH2CH3
OCH2C6CH5
CH3


104
OCH2CH2CO2H
OCH2C6CH5
CH3


105
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
H


106
OCH2CH2PO(OH)2
OCH2C6CH5
H


107 
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
CH3


108
OCH2CH2PO(OH)2
OCH2C6CH5
CH3


109
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
H


110
OCH2CH═CHCO2H
OCH2C6CH5
H


111
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
CH3


112
OCH2CH═CHCO2H
OCH2C6CH5
CH3


113
OCH2CO2CH2CH3
OCH2CONH2
H


114
OCH2CO2H
OCH2CONH2
H


115
OCH2CO2CH2CH3
OCH2CONH2
CH3


116
OCH2CO2H
OCH2CONH2
CH3


117
OCH2CH2CO2CH2CH3
OCH2CONH2
H


118
OCH2CH2CO2H
OCH2CONH2
H


119
OCH2CH2CO2CH2CH3
OCH2CONH2
CH3


120
OCH2CH2CO2H
OCH2CONH2
CH3


121
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
H


122
OCH2CH2PO(OH)2
OCH2CONH2
H


123
OCH2CH2PO(OCH2CH3)2
OCH2CONH2 
CH3


124
OCH2CH2PO(OH)2
OCH2CONH2 
CH3


125
OCH2CH═CHCO2CH2CH3
OCH2CONH2 
H


126
OCH2CH═CHCO2H
OCH2CONH2 
H


127
OCH2CH═CHCO2CH2CH3
OCH2CONH2 
CH3


128
OCH2CH═CHCO2H
OCH2CONH2 
CH3


159
OCH2CH2—N+(CH3)3 X−
H
H


160
OCH2CH2—N+(CH3)3 X−
H
CH3


161
OCH2CH2—N+(CH3)3 X−
OCH3
H


162
OCH2CH2—N+(CH3)3 X−
OCH3
CH3


163
OCH2CH2—N+(CH3)3 X−
OCH2CH═CH2
H


164
OCH2CH2—N+(CH3)3 X−
OCH2CH═CH2
CH3


165
OCH2CH2—N+(CH3)3 X−
OCH2C6CH5 
H


166
OCH2CH2—N+(CH3)3 X−
OCH2C6CH5 
CH3
















TABLE IVb













 










Ex.





#
X1
Z
R1













1
OCH2CO2CH2CH3
H
H


2
OCH2CO2H
H
H


3
OCH2CO2CH2CH3
H
CH3


4
OCH2CO2H
H
CH3


5
OCH2CH2CO2CH2CH3
H
H


6
OCH2CH2CO2H
H
H


7
OCH2CH2CO2CH2CH3
H
CH3


8
OCH2CH2CO2H
H
CH3


9
OCH2CH2PO(OCH2CH3)2
H
H


10
OCH2CH2PO(OH)2
H
H


11
OCH2CH2PO(OCH2CH3)2
H
CH3


12
OCH2CH2PO(OH)2
H
CH3


13
OCH2CH═CHCO2CH2CH3
H
H


14
OCH2CH═CHCO2H
H
H


15
OCH2CH═CHCO2CH2CH3
H
CH3


16
OCH2CH═CHCO2H
H
CH3


17
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
H
H


18
OCH2C6H4CO2H (2, 3 or 4)
H
H


19
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
H
CH3


20
OCH2C6H4CO2H (2, 3 or 4)
H
CH3


21
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
H
H


22
OCH2C6H4CH2CO2H (2, 3 or 4)
H
H


23
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
H
CH3


24
OCH2C6H4CH2CO2H (2, 3 or 4)
H
CH3


25
OCH2CO2CH2CH3
OH
H


26
OCH2CO2H
OH
H


27
OCH2CO2CH2CH3
OH
CH3


28
OCH2CO2H
OH
CH3


29
OCH2CH2CO2CH2CH3
OH
H


30
OCH2CH2CO2H
OH
H


31
OCH2CH2CO2CH2CH3
OH
CH3


32
OCH2CH2CO2H
OH
CH3


33
OCH2CH2PO(OCH2CH3)2
OH
H


34
OCH2CH2PO(OH)2
OH
H


35
OCH2CH2PO(OCH2CH3)2
OH
CH3


36
OCH2CH2PO(OH)2
OH
CH3


37
OCH2CH═CHCO2CH2CH3
OH
H


38
OCH2CH═CHCO2H
OH
H


39
OCH2CH═CHCO2CH2CH3
OH
CH3


40
OCH2CH═CHCO2H
OH
CH3


41
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OH
H


42
OCH2C6H4CO2H (2, 3 or 4)
OH
H


43
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OH
CH3


44
OCH2C6H4CO2H (2, 3 or 4)
OH
CH3


45
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OH
H


46
OCH2C6H4CH2CO2H (2, 3 or 4)
OH
H


47
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OH
CH3


48
OCH2C6H4CH2CO2H (2, 3 or 4)
OH
CH3


49
OCH2CO2CH2CH3
OCH3
H


50
OCH2CO2H
OCH3
H


51
OCH2CO2CH2CH3
OCH3
CH3


52
OCH2CO2H
OCH3
CH3


53
OCH2CH2CO2CH2CH3
OCH3
H


54
OCH2CH2CO2H
OCH3
H


55
OCH2CH2CO2CH2CH3
OCH3
CH3


56
OCH2CH2CO2H
OCH3
CH3


57
OCH2CH2PO(OCH2CH3)2
OCH3
H


58
OCH2CH2PO(OH)2
OCH3
H


59
OCH2CH2PO(OCH2CH3)2
OCH3
CH3


60
OCH2CH2PO(OH)2
OCH3
CH3


61
OCH2CH═CHCO2CH2CH3
OCH3
H


62
OCH2CH═CHCO2H
OCH3
H


63
OCH2CH═CHCO2CH2CH3
OCH3
CH3


64
OCH2CH═CHCO2H
OCH3
CH3


65
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH3
H


66
OCH2C6H4CO2H (2, 3 or 4)
OCH3
H


67
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH3
CH3


68
OCH2C6H4CO2H (2, 3 or 4)
OCH3
CH3


69
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OCH3
H


70
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH3
H


71
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OCH3
CH3


72
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH3
CH3


73
OCH2CO2CH2CH3
OCH2CH═CH2
H


74
OCH2CO2H
OCH2CH═CH2
H


75
OCH2CO2CH2CH3
OCH2CH═CH2
CH3


76
OCH2CO2H
OCH2CH═CH2
CH3


77
OCH2CH2CO2CH2CH3
OCH2CH═CH2
H


78
OCH2CH2CO2H
OCH2CH═CH2
H


79
OCH2CH2CO2CH2CH3
OCH2CH═CH2
CH3


80
OCH2CH2CO2H
OCH2CH═CH2
CH3


81
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
H


82
OCH2CH2PO(OH)2
OCH2CH═CH2
H


83
OCH2CH2PO(OCH2CH3)2
OCH2CH═CH2
CH3


84
OCH2CH2PO(OH)2
OCH2CH═CH2
CH3


85
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
H


86
OCH2CH═CHCO2H
OCH2CH═CH2
H


87
OCH2CH═CHCO2CH2CH3
OCH2CH═CH2
CH3


88
OCH2CH═CHCO2H
OCH2CH═CH2
CH3


89
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
H


90
OCH2C6H4CO2H (2, 3 or 4)
OCH2CH═CH2
H


91
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
CH3


92
OCH2C6H4CO2H (2, 3 or 4)
OCH2CH═CH2
CH3


93
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
H


94
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH2CH═CH2
H


95
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
OCH2CH═CH2
CH3


96
OCH2C6H4CH2CO2H (2, 3 or 4)
OCH2CH═CH2
CH3


97
OCH2CO2CH2CH3
OCH2C6CH5
H


98
OCH2CO2H
OCH2C6CH5
H


99
OCH2CO2CH2CH3
OCH2C6CH5
CH3


100
OCH2CO2H
OCH2C6CH5
CH3


101
OCH2CH2CO2CH2CH3
OCH2C6CH5
H


102
OCH2CH2CO2H
OCH2C6CH5
H


103
OCH2CH2CO2CH2CH3
OCH2C6CH5
CH3


104
OCH2CH2CO2H
OCH2C6CH5
CH3


105
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
H


106
OCH2CH2PO(OH)2
OCH2C6CH5
H


107
OCH2CH2PO(OCH2CH3)2
OCH2C6CH5
CH3


108
OCH2CH2PO(OH)2
OCH2C6CH5
CH3


109
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
H


110
OCH2CH═CHCO2H
OCH2C6CH5
H


111
OCH2CH═CHCO2CH2CH3
OCH2C6CH5
CH3


112
OCH2CH═CHCO2H
OCH2C6CH5
CH3


113
OCH2CO2CH2CH3
OCH2CONH2
H


114
OCH2CO2H
OCH2CONH2
H


115
OCH2CO2CH2CH3
OCH2CONH2
CH3


116
OCH2CO2H
OCH2CONH2
CH3


117
OCH2CH2CO2CH2CH3
OCH2CONH2
H


118
OCH2CH2CO2H
OCH2CONH2
H


119
OCH2CH2CO2CH2CH3
OCH2CONH2
CH3


120
OCH2CH2CO2H
OCH2CONH2
CH3


121
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
H


122
OCH2CH2PO(OH)2
OCH2CONH2
H


123
OCH2CH2PO(OCH2CH3)2
OCH2CONH2
CH3


124
OCH2CH2PO(OH)2
OCH2CONH2
CH3


125
OCH2CH═CHCO2CH2CH3
OCH2CONH2
H


126
OCH2CH═CHCO2H
OCH2CONH2
H


127
OCH2CH═CHCO2CH2CH3
OCH2CONH2
CH3


128
OCH2CH═CHCO2H
OCH2CONH2
CH3


159
OCH2CH2—N+(CH3)3 X−
H
H


160
OCH2CH2—N+(CH3)3 X−
H
CH3


161
OCH2CH2—N+(CH3)3 X−
OCH3
H


162
OCH2CH2—N+(CH3)3 X−
OCH3
CH3


163
OCH2CH2—N+(CH3)3 X−
OCH2CH═CH2
H


164
OCH2CH2—N+(CH3)3 X−
OCH2CH═CH2
CH3


165
OCH2CH2—N+(CH3)3 X−
OCH2C6CH5
H


166
OCH2CH2—N+(CH3)3 X−
OCH2C6CH5
CH3
















TABLE IVc













 










Ex.





#
X
Z
R1













1
OCH2CO2H
N(CH3)2
H


2
OCH2CO2CH2CH3
N(CH3)2
CH3


3
OCH2CO2H
N(CH3)2
CH3


4
OCH2CH2CO2CH2CH3
N(CH3)2
H


5
OCH2CH2CO2H
N(CH3)2
H


6
OCH2CH2CO2CH2CH3
N(CH3)2
CH3


7
OCH2CH2CO2H
N(CH3)2
CH3


8
OCH2CH2PO(OCH2CH3)2
N(CH3)2
H


9
OCH2CH2PO(OH)2
N(CH3)2
H


10
OCH2CH2PO(OCH2CH3)2
N(CH3)2
CH3


11
OCH2CH2PO(OH)2
N(CH3)2
CH3


12
OCH2CH═CHCO2CH2CH3
N(CH3)2
H


13
OCH2CH═CHCO2H
N(CH3)2
H


14
OCH2CH═CHCO2CH2CH3
N(CH3)2
CH3


15
OCH2CH═CHCO2H
N(CH3)2
CH3


16
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
N(CH3)2
H


17
OCH2C6H4CO2H (2, 3 or 4)
N(CH3)2
H


18
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
N(CH3)2
CH3


19
OCH2C6H4CO2H (2, 3 or 4)
N(CH3)2
CH3


20
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
N(CH3)2
H


21
OCH2C6H4CH2CO2H (2, 3 or 4)
N(CH3)2
H


22
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
N(CH3)2
CH3


23
OCH2C6H4CH2CO2H (2, 3 or 4)
N(CH3)2
CH3


24
OCH2CO2CH2CH3
NHCH2C6CH5
H


25
OCH2CO2H
NHCH2C6CH5
H


26
OCH2CO2CH2CH3
NHCH2C6CH5
CH3


27
OCH2CO2H
NHCH2C6CH5
CH3


28
OCH2CH2CO2CH2CH3
NHCH2C6CH5
H


29
OCH2CH2CO2H
NHCH2C6CH5
H


30
OCH2CH2CO2CH2CH3
NHCH2C6CH5
CH3


31
OCH2CH2CO2H
NHCH2C6CH5
CH3


32
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
H


33
OCH2CH2PO(OH)2
NHCH2C6CH5
H


34
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
CH3


35
OCH2CH2PO(OH)2
NHCH2C6CH5
CH3


36
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
H


37
OCH2CH═CHCO2H
NHCH2C6CH5
H


38
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
CH3


39
OCH2CH═CHCO2H
NHCH2C6CH5
CH3


40
OCH2CO2CH2CH3
NHCH2CONH2
H


41
OCH2CO2H
NHCH2CONH2
H


42
OCH2CO2CH2CH3
NHCH2CONH2
CH3


43
OCH2CO2H
NHCH2CONH2
CH3


44
OCH2CH2CO2CH2CH3
NHCH2CONH2
H


45
OCH2CH2CO2H
NHCH2CONH2
H


46
OCH2CH2CO2CH2CH3
NHCH2CONH2
CH3


47
OCH2CH2CO2H
NHCH2CONH2
CH3


48
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
H


49
OCH2CH2PO(OH)2
NHCH2CONH2
H


50
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
CH3


51
OCH2CH2PO(OH)2
NHCH2CONH2
CH3


52
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
H


53
OCH2CH═CHCO2H
NHCH2CONH2
H


54
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
CH3


55
OCH2CH═CHCO2H
NHCH2CONH2
CH3


56
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
H


57
OCH2C6H4CO2H (2, 3 or 4)
NHCH2CONH2
H


58
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
CH3


59
OCH2C6H4CO2H (2, 3 or 4)
NHCH2CONH2
CH3


60
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
H


61
OCH2C6H4CH2CO2H (2, 3 or 4)
NHCH2CONH2
H


62
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
CH3


63
OCH2C6H4CH2CO2H (2, 3 or 4)
NHCH2CONH2
CH3
















TABLE IVd













 










Ex.





#
X1
Z
R1













1
OCH2CO2H
N(CH3)2
H


2
OCH2CO2CH2CH3
N(CH3)2
CH3


3
OCH2CO2H
N(CH3)2
CH3


4
OCH2CH2CO2CH2CH3
N(CH3)2
H


5
OCH2CH2CO2H
N(CH3)2
H


6
OCH2CH2CO2CH2CH3
N(CH3)2
CH3


7
OCH2CH2CO2H
N(CH3)2
CH3


8
OCH2CH2PO(OCH2CH3)2
N(CH3)2
H


9
OCH2CH2PO(OH)2
N(CH3)2
H


10
OCH2CH2PO(OCH2CH3)2
N(CH3)2
CH3


11
OCH2CH2PO(OH)2
N(CH3)2
CH3


12
OCH2CH═CHCO2CH2CH3
N(CH3)2
H


13
OCH2CH═CHCO2H
N(CH3)2
H


14
OCH2CH═CHCO2CH2CH3
N(CH3)2
CH3


15
OCH2CH═CHCO2H
N(CH3)2
CH3


16
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
N(CH3)2
H


17
OCH2C6H4CO2H (2, 3 or 4)
N(CH3)2
H


18
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
N(CH3)2
CH3


19
OCH2C6H4CO2H (2, 3 or 4)
N(CH3)2
CH3


20
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
N(CH3)2
H


21
OCH2C6H4CH2CO2H (2, 3 or 4)
N(CH3)2
H


22
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
N(CH3)2
CH3


23
OCH2C6H4CH2CO2H (2, 3 or 4)
N(CH3)2
CH3


24
OCH2CO2CH2CH3
NHCH2C6CH5
H


25
OCH2CO2H
NHCH2C6CH5
H


26
OCH2CO2CH2CH3
NHCH2C6CH5
CH3


27
OCH2CO2H
NHCH2C6CH5
CH3


28
OCH2CH2CO2CH2CH3
NHCH2C6CH5
H


29
OCH2CH2CO2H
NHCH2C6CH5
H


30
OCH2CH2CO2CH2CH3
NHCH2C6CH5
CH3


31
OCH2CH2CO2H
NHCH2C6CH5
CH3


32
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
H


33
OCH2CH2PO(OH)2
NHCH2C6CH5
H


34
OCH2CH2PO(OCH2CH3)2
NHCH2C6CH5
CH3


35
OCH2CH2PO(OH)2
NHCH2C6CH5
CH3


36
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
H


37
OCH2CH═CHCO2H
NHCH2C6CH5
H


38
OCH2CH═CHCO2CH2CH3
NHCH2C6CH5
CH3


39
OCH2CH═CHCO2H
NHCH2C6CH5
CH3


40
OCH2CO2CH2CH3
NHCH2CONH2
H


41
OCH2CO2H
NHCH2CONH2
H


42
OCH2CO2CH2CH3
NHCH2CONH2
CH3


43
OCH2CO2H
NHCH2CONH2
CH3


44
OCH2CH2CO2CH2CH3
NHCH2CONH2
H


45
OCH2CH2CO2H
NHCH2CONH2
H


46
OCH2CH2CO2CH2CH3
NHCH2CONH2
CH3


47
OCH2CH2CO2H
NHCH2CONH2
CH3


48
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
H


49
OCH2CH2PO(OH)2
NHCH2CONH2
H


50
OCH2CH2PO(OCH2CH3)2
NHCH2CONH2
CH3


51
OCH2CH2PO(OH)2
NHCH2CONH2
CH3


52
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
H


53
OCH2CH═CHCO2H
NHCH2CONH2
H


54
OCH2CH═CHCO2CH2CH3
NHCH2CONH2
CH3


55
OCH2CH═CHCO2H
NHCH2CONH2
CH3


56
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
H


57
OCH2C6H4CO2H (2, 3 or 4)
NHCH2CONH2
H


58
OCH2C6H4CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
CH3


59
OCH2C6H4CO2H (2, 3 or 4)
NHCH2CONH2
CH3


60
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
H


61
OCH2C6H4CH2CO2H (2, 3 or 4)
NHCH2CONH2
H


62
OCH2C6H4CH2CO2CH2CH3 (2, 3 or 4)
NHCH2CONH2
CH3


63
OCH2C6H4CH2CO2H (2, 3 or 4)
NHCH2CONH2
CH3
















TABLE V













 











Ex. #
X
X1
Z
R1














1.
H
H
OH
CO2CH2CH3


2.
H
H
OH
CO2H


3.
H
H
OH
CH2CO2CH2CH3


4.
H
H
OH
CH2CO2H


5.
H
H
OH
CH2CH2CO2CH2CH3


6.
H
H
OH
CH2CH2CO2H


7.
H
H
OH
CH2CH═CHCO2H


8.
H
H
OH
CH2CH═CHCO2H


9.
H
H
OH
CH2CH2P—O(OCH2CH3)2


10.
H
H
OH
CH2CH2P—O(OH)2


11.
OH
H
OH
CO2CH2CH3


12.
OH
H
OH
CO2H


13.
OH
H
OH
CH2CO2CH2CH3


14.
OH
H
OH
CH2CO2H


15.
OH
H
OH
CH2CH2CO2CH2CH3


16.
OH
H
OH
CH2CH2CO2H


17.
OH
H
OH
CH2CH═CHCO2H


18.
OH
H
OH
CH2CH═CHCO2H


19.
OH
H
OH
CH2CH2P—O(OCH2CH3)2


20.
OH
H
OH
CH2CH2P—O(OH)2


21.
OCH3
H
OH
CO2CH2CH3


22.
OCH3
H
OH
CO2H


23.
OCH3
H
OH
CH2CO2CH2CH3


24.
OCH3
H
OH
CH2CO2H


25.
OCH3
H
OH
CH2CH2CO2CH2CH3


26.
OCH3
H
OH
CH2CH2CO2H


27.
OCH3
H
OH
CH2CH═CHCO2H


28.
OCH3
H
OH
CH2CH═CHCO2H


29.
OCH3
H
OH
CH2CH2P—O(OCH2CH3)2


30.
OCH3
H
OH
CH2CH2P—O(OH)2


31.
OCH2CH═CH2
H
OH
CO2CH2CH3


32.
OCH2CH═CH2
H
OH
CO2H


33.
OCH2CH═CH2
H
OH
CH2CO2CH2CH3


34.
OCH2CH═CH2
H
OH
CH2CO2H


35.
OCH2CH═CH2
H
OH
CH2CH2CO2CH2CH3


36.
OCH2CH═CH2
H
OH
CH2CH2CO2H


37.
OCH2CH═CH2
H
OH
CH2CH═CHCO2H


38.
OCH2CH═CH2
H
OH
CH2CH═CHCO2H


39.
OCH2CH═CH2
H
OH
CH2CH2P—O(OCH2CH3)2


40.
OCH2CH═CH2
H
OH
CH2CH2P—O(OH)2


41.
OCH2C6H5
H
OH
CO2CH2CH3


42.
OCH2C6H5
H
OH
CO2H


43.
OCH2C6H5
H
OH
CH2CO2CH2CH3


44.
OCH2C6H5
H
OH
CH2CO2H


45.
OCH2C6H5
H
OH
CH2CH2CO2CH2CH3


46.
OCH2C6H5
H
OH
CH2CH2CO2H


47.
OCH2C6H5
H
OH
CH2CH═CHCO2H


48.
OCH2C6H5
H
OH
CH2CH═CHCO2H


49.
OCH2C6H5
H
OH
CH2CH2P—O(OCH2CH3)2


50.
OCH2C6H5
H
OH
CH2CH2P—O(OH)2


51.
Cl
H
OH
CO2CH2CH3


52.
Cl
H
OH
CO2H


53.
Cl
H
OH
CH2CO2CH2CH3


54.
Cl
H
OH
CH2CO2H


55.
Cl
H
OH
CH2CH2CO2CH2CH3


56.
Cl
H
OH
CH2CH2CO2H


57.
Cl
H
OH
CH2CH═CHCO2H


58.
Cl
H
OH
CH2CH═CHCO2H


59.
Cl
H
OH
CH2CH2P—O(OCH2CH3)2


60.
Cl
H
OH
CH2CH2P—O(OH)2


61.
NO2
H
OH
CO2CH2CH3


62.
NO2
H
OH
CO2H


63.
NO2
H
OH
CH2CO2CH2CH3


64.
NO2
H
OH
CH2CO2H


65.
NO2
H
OH
CH2CH2CO2CH2CH3


66.
NO2
H
OH
CH2CH2CO2H


67.
NO2
H
OH
CH2CH═CHCO2H


68.
NO2
H
OH
CH2CH═CHCO2H


69.
NO2
H
OH
CH2CH2P—O(OCH2CH3)2


70.
NO2
H
OH
CH2CH2P—O(OH)2


71.
NHSO2CH3
H
OH
H


72.
NHSO2CH3
H
OH
CH3


73.
NHSO2CH3
H
OH
CO2CH2CH3


74.
NHSO2CH3
H
OH
CO2H


75.
NHSO2CH3
H
OH
CH2CO2CH2CH3


76.
NHSO2CH3
H
OH
CH2CO2H


77.
NHSO2CH3
H
OH
CH2CH2CO2CH2CH3


78.
NHSO2CH3
H
OH
CH2CH2CO2H


79.
NHSO2CH3
H
OH
CH2CH═CHCO2H


80.
NHSO2CH3
H
OH
CH2CH═CHCO2H


81.
NHSO2CH3
H
OH
CH2CH2P—O(OCH2CH3)2


82.
NHSO2CH3
H
OH
CH2CH2P—O(OH)2


83.
OCH2CONH2
H
OH
H


84.
OCH2CONH2
H
OH
CH3


85.
OCH2CONH2
H
OH
CO2CH2CH3


86.
OCH2CONH2
H
OH
CO2H


87.
OCH2CONH2
H
OH
CH2CO2CH2CH3


88.
OCH2CONH2
H
OH
CH2CO2H


89.
OCH2CONH2
H
OH
CH2CH2CO2CH2CH3


90.
OCH2CONH2
H
OH
CH2CH2CO2H


91.
OCH2CONH2
H
OH
CH2CH═CHCO2H


92.
OCH2CONH2
H
OH
CH2CH═CHCO2H


93.
OCH2CONH2
H
OH
CH2CH2P—O(OCH2CH3)2


94.
OCH2CONH2
H
OH
CH2CH2P—O(OH)2


95.
OH
CH2N(CH3)2
OH
CO2CH2CH3


96.
OH
CH2N(CH3)2
OH
CO2H


97.
OH
CH2N(CH3)2
OH
CH2CO2CH2CH3


98.
OH
CH2N(CH3)2
OH
CH2CO2H


99.
OH
CH2N(CH3)2
OH
CH2CH2CO2CH2CH3


100.
OH
CH2N(CH3)2
OH
CH2CH2CO2H


101.
OH
CH2N(CH3)2
OH
CH2CH═CHCO2H


102.
OH
CH2N(CH3)2
OH
CH2CH═CHCO2H


103.
OH
CH2N(CH3)2
OH
CH2CH2P—O(OCH2CH3)2


104.
OH
CH2N(CH3)2
OH
CH2CH2P—O(OH)2


105.
OCH3
CH2N(CH3)2
OH
CO2CH2CH3


106.
OCH3
CH2N(CH3)2
OH
CO2H


107.
OCH3
CH2N(CH3)2
OH
CH2CO2CH2CH3


108.
OCH3
CH2N(CH3)2
OH
CH2CO2H


109.
OCH3
CH2N(CH3)2
OH
CH2CH2CO2CH2CH3


110.
OCH3
CH2N(CH3)2
OH
CH2CH2CO2H


111.
OCH3
CH2N(CH3)2
OH
CH2CH═CHCO2H


112.
OCH3
CH2N(CH3)2
OH
CH2CH═CHCO2H


113.
OCH3
CH2N(CH3)2
OH
CH2CH2P—O(OCH2CH3)2


114.
OCH3
CH2N(CH3)2
OH
CH2CH2P—O(OH)2


115.
OH
CH2N+(CH3)3
OH
H




Cl−




116.
OH
CH2N+(CH3)3
OH
CH3




Cl−




117.
OH
CH2N+(CH3)3
OH
CO2CH2CH3




Cl−




118.
OH
CH2N+(CH3)3
OH
CO2H




Cl−




119.
OH
CH2N+(CH3)3
OH
CH2CO2CH2CH3




Cl−




120.
OH
CH2N+(CH3)3
OH
CH2CO2H




Cl−




121.
OH
CH2N+(CH3)3
OH
CH2CH2CO2CH2CH3




Cl−




122.
OH
CH2N+(CH3)3
OH
CH2CH2CO2H




Cl−




123.
OH
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




124.
OH
CH2N+(CH3)3
OH
CH2CH═CHCO2H




Cl−




125.
OH
CH2N+(CH3)3
OH
CH2CH2P—O(OCH2CH3)2




Cl−




126.
OH
CH2N+(CH3)3
OH
CH2CH2P—O(OH)2




Cl−




127.
OCH3
CH2N+(CH3)3 
OH
H




Cl−




128.
OCH3
CH2N+(CH3)3 
OH
CH3




Cl−




129.
OCH3
CH2N+(CH3)3 
OH
CO2CH2CH3




Cl−




130.
OCH3
CH2N+(CH3)3 
OH
CO2H




Cl−




131.
OCH3
CH2N+(CH3)3 
OH
CH2CO2CH2CH3




Cl−




132.
OCH3
CH2N+(CH3)3 
OH
CH2CO2H




Cl−




133.
OCH3
CH2N+(CH3)3 
OH
CH2CH2CO2CH2CH3




Cl−




134.
OCH3
CH2N+(CH3)3 
OH
CH2CH2CO2H




Cl−




135.
OCH3
CH2N+(CH3)3 
OH
CH2CH═CHCO2H




Cl−




136.
OCH3
CH2N+(CH3)3 
OH
CH2CH═CHCO2H




Cl−




137.
OCH3
CH2N+(CH3)3 
OH
CH2CH2P—O(OCH2CH3)2




Cl−




138.
OCH3
CH2N+(CH3)3 
OH
CH2CH2P—O(OH)2




Cl−




139 .
H
H
OCH3
CO2CH2CH3


140.
H
H
OCH3
CO2H


141.
H
H
OCH3
CH2CO2CH2CH3


142.
H
H
OCH3
CH2CO2H


143.
H
H
OCH3
CH2CH2CO2CH2CH3


144.
H
H
OCH3
CH2CH2CO2H


145.
H
H
OCH3
CH2CH═CHCO2H


146.
H
H
OCH3
CH2CH═CHCO2H


147.
H
H
OCH3
CH2CH2P—O(OCH2CH3)2


148.
H
H
OCH3
CH2CH2P—O(OH)2


149.
OH
H
OCH3
CO2CH2CH3


150.
OH
H
OCH3
CO2H


151.
OH
H
OCH3
CH2CO2CH2CH3


152.
OH
H
OCH3
CH2CO2H


153.
OH
H
OCH3
CH2CH2CO2CH2CH3


154.
OH
H
OCH3
CH2CH2CO2H


155.
OH
H
OCH3
CH2CH═CHCO2H


156.
OH
H
OCH3
CH2CH═CHCO2H


157.
OH
H
OCH3
CH2CH2P—O(OCH2CH3)2


158.
OH
H
OCH3
CH2CH2P—O(OH)2


159.
OCH3
H
OCH3
CO2CH2CH3


160.
OCH3
H
OCH3
CO2H


161.
OCH3
H
OCH3
CH2CO2CH2CH3


162.
OCH3
H
OCH3
CH2CO2H


163.
OCH3
H
OCH3
CH2CH2CO2CH2CH3


164.
OCH3
H
OCH3
CH2CH2CO2H


165.
OCH3
H
OCH3
CH2CH═CHCO2H


166.
OCH3
H
OCH3
CH2CH═CHCO2H


167.
OCH3
H
OCH3
CH2CH2P—O(OCH2CH3)2


168.
OCH3
H
OCH3
CH2CH2P—O(OH)2


169.
OCH2CH═CH2
H
OCH3
CO2CH2CH3


170.
OCH2CH═CH2
H
OCH3
CO2H


171.
OCH2CH═CH2
H
OCH3
CH2CO2CH2CH3


172.
OCH2CH═CH2
H
OCH3
CH2CO2H


173.
OCH2CH═CH2
H
OCH3
CH2CH2CO2CH2CH3


174.
OCH2CH═CH2
H
OCH3
CH2CH2CO2H


175.
OCH2CH═CH2
H
OCH3
CH2CH═CHCO2H


176.
OCH2CH═CH2
H
OCH3
CH2CH═CHCO2H


177.
OCH2CH═CH2
H
OCH3
CH2CH2P—O(OCH2CH3)2


178.
OCH2CH═CH2
H
OCH3
CH2CH2P—O(OH)2


179.
OCH2C6H5
H
OCH3
CO2CH2CH3


180.
OCH2C6H5
H
OCH3
CO2H


181.
OCH2C6H5
H
OCH3
CH2CO2CH2CH3


182.
OCH2C6H5
H
OCH3
CH2CO2H


183.
OCH2C6H5
H
OCH3
CH2CH2CO2CH2CH3


184.
OCH2C6H5
H
OCH3
CH2CH2CO2H


185.
OCH2C6H5
H
OCH3
CH2CH═CHCO2H


186.
OCH2C6H5
H
OCH3
CH2CH═CHCO2H


187.
OCH2C6H5
H
OCH3
CH2CH2P—O(OCH2CH3)2


188.
OCH2C6H5
H
OCH3
CH2CH2P—O(OH)2


189.
Cl
H
OCH3
CO2CH2CH3


190.
Cl
H
OCH3
CO2H


191.
Cl
H
OCH3
CH2CO2CH2CH3


192.
Cl
H
OCH3
CH2CO2H


193.
Cl
H
OCH3
CH2CH2CO2CH2CH3


194.
Cl
H
OCH3
CH2CH2CO2H


195.
Cl
H
OCH3
CH2CH═CHCO2H


196.
Cl
H
OCH3
CH2CH═CHCO2H


197.
Cl
H
OCH3
CH2CH2P—O(OCH2CH3)2


198.
Cl
H
OCH3
CH2CH2P—O(OH)2


199.
NO2
H
OCH3
CO2CH2CH3


200.
NO2
H
OCH3
CO2H


201.
NO2
H
OCH3
CH2CO2CH2CH3


202.
NO2
H
OCH3
CH2CO2H


203.
NO2
H
OCH3
CH2CH2CO2CH2CH3


204.
NO2
H
OCH3
CH2CH2CO2H


205.
NO2
H
OCH3
CH2CH═CHCO2H


206.
NO2
H
OCH3
CH2CH═CHCO2H


207.
NO2
H
OCH3
CH2CH2P—O(OCH2CH3)2


208.
NO2
H
OCH3
CH2CH2P—O(OH)2


209.
NHSO2CH3
H
OCH3
H


210.
NHSO2CH3
H
OCH3
CH3


211.
NHSO2CH3
H
OCH3
CO2CH2CH3


212.
NHSO2CH3
H
OCH3
CO2H


213.
NHSO2CH3
H
OCH3
CH2CO2CH2CH3


214.
NHSO2CH3
H
OCH3
CH2CO2H


215.
NHSO2CH3
H
OCH3
CH2CH2CO2CH2CH3


216.
NHSO2CH3
H
OCH3
CH2CH2CO2H


217.
NHSO2CH3
H
OCH3
CH2CH═CHCO2H


218.
NHSO2CH3
H
OCH3
CH2CH═CHCO2H


219.
NHSO2CH3
H
OCH3
CH2CH2P—O(OCH2CH3)2


220.
NHSO2CH3
H
OCH3
CH2CH2P—O(OH)2


221.
OCH2CONH2
H
OCH3
H


222.
OCH2CONH2
H
OCH3
CH3


223.
OCH2CONH2
H
OCH3
CO2CH2CH3


224.
OCH2CONH2
H
OCH3
CO2H


225.
OCH2CONH2
H
OCH3
CH2CO2CH2CH3


226.
OCH2CONH2
H
OCH3
CH2CO2H


227.
OCH2CONH2
H
OCH3
CH2CH2CO2CH2CH3


228.
OCH2CONH2
H
OCH3
CH2CH2CO2H


229.
OCH2CONH2
H
OCH3
CH2CH═CHCO2H


230.
OCH2CONH2
H
OCH3
CH2CH═CHCO2H


231.
OCH2CONH2
H
OCH3
CH2CH2P—O(OCH2CH3)2


232.
OCH2CONH2
H
OCH3
CH2CH2P—O(OH)2


233.
OH
CH2N(CH3)2
OCH3
CO2CH2CH3


234.
OH
CH2N(CH3)2
OCH3
CO2H


235.
OH
CH2N(CH3)2
OCH3
CH2CO2CH2CH3


236.
OH
CH2N(CH3)2
OCH3
CH2CO2H


237.
OH
CH2N(CH3)2
OCH3
CH2CH2CO2CH2CH3


238.
OH
CH2N(CH3)2
OCH3
CH2CH2CO2H


239.
OH
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


240.
OH
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


241.
OH
CH2N(CH3)2
OCH3
CH2CH2P—O(OCH2CH3)2


242.
OH
CH2N(CH3)2
OCH3
CH2CH2P—O(OH)2


243.
OCH3
CH2N(CH3)2
OCH3
CO2CH2CH3


244.
OCH3
CH2N(CH3)2
OCH3
CO2H


245.
OCH3
CH2N(CH3)2
OCH3
CH2CO2CH2CH3


246.
OCH3
CH2N(CH3)2
OCH3
CH2CO2H


247.
OCH3
CH2N(CH3)2
OCH3
CH2CH2CO2CH2CH3


248.
OCH3
CH2N(CH3)2
OCH3
CH2CH2CO2H


249.
OCH3
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


250.
OCH3
CH2N(CH3)2
OCH3
CH2CH═CHCO2H


251.
OCH3
CH2N(CH3)2
OCH3
CH2CH2P—O(OCH2CH3)2


252.
OCH3
CH2N(CH3)2
OCH3
CH2CH2P—O(OH)2


253.
OH
CH2N+(CH3)3
OCH3
H




Cl−




254.
OH
CH2N+(CH3)3
OCH3
CH3




Cl−




255.
OH
CH2N+(CH3)3
OCH3
CO2CH2CH3




Cl−




256.
OH
CH2N+(CH3)3
OCH3
CO2H




Cl−




257.
OH
CH2N+(CH3)3
OCH3
CH2CO2CH2CH3




Cl−




258.
OH
CH2N+(CH3)3
OCH3
CH2CO2H




Cl−




259.
OH
CH2N+(CH3)3
OCH3
CH2CH2CO2CH2CH3




Cl−




260.
OH
CH2N+(CH3)3
OCH3
CH2CH2CO2H




Cl−




261.
OH
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




262.
OH
CH2N+(CH3)3
OCH3
CH2CH═CHCO2H




Cl−




263.
OH
CH2N+(CH3)3
OCH3
CH2CH2P—O(OCH2CH3)2




Cl−




264.
OH
CH2N+(CH3)3
OCH3
CH2CH2P—O(OH)2




Cl−




265.
OCH3
CH2N+(CH3)3 
OCH3
H




Cl−




266.
OCH3
CH2N+(CH3)3 
OCH3
CH3




Cl−




267.
OCH3
CH2N+(CH3)3 
OCH3
CO2CH2CH3




Cl−




268.
OCH3
CH2N+(CH3)3 
OCH3
CO2H




Cl−




269.
OCH3
CH2N+(CH3)3 
OCH3
CH2CO2CH2CH3




Cl−




270.
OCH3
CH2N+(CH3)3 
OCH3
CH2CO2H




Cl−




271.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH2CO2CH2CH3




Cl−




272.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH2CO2H




Cl−




273.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH═CHCO2H




Cl−




274.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH═CHCO2H




Cl−




275.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH2P—O(OCH2CH3)2




Cl−




276.
OCH3
CH2N+(CH3)3 
OCH3
CH2CH2P—O(OH)2




Cl−




277.
H
H
OCH2C6H5
CO2CH2CH3


278.
H
H
OCH2C6H5
CO2H


279.
H
H
OCH2C6H5
CH2CO2CH2CH3


280.
H
H
OCH2C6H5
CH2CO2H


281.
H
H
OCH2C6H5
CH2CH2CO2CH2CH3


282.
H
H
OCH2C6H5
CH2CH2CO2H


283.
H
H
OCH2C6H5
CH2CH═CHCO2H


284.
H
H
OCH2C6H5
CH2CH═CHCO2H


285.
H
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


286.
H
H
OCH2C6H5
CH2CH2P—O(OH)2


287.
OH
H
OCH2C6H5
CO2CH2CH3


288.
OH
H
OCH2C6H5
CO2H


289.
OH
H
OCH2C6H5
CH2CO2CH2CH3


290.
OH
H
OCH2C6H5
CH2CO2H


291.
OH
H
OCH2C6H5
CH2CH2CO2CH2CH3


292.
OH
H
OCH2C6H5
CH2CH2CO2H


293.
OH
H
OCH2C6H5
CH2CH═CHCO2H


294.
OH
H
OCH2C6H5
CH2CH═CHCO2H


295.
OH
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


296.
OH
H
OCH2C6H5
CH2CH2P—O(OH)2


297.
OCH3
H
OCH2C6H5
CO2CH2CH3


298.
OCH3
H
OCH2C6H5
CO2H


299.
OCH3
H
OCH2C6H5
CH2CO2CH2CH3


300.
OCH3
H
OCH2C6H5
CH2CO2H


301.
OCH3
H
OCH2C6H5
CH2CH2CO2CH2CH3


302.
OCH3
H
OCH2C6H5
CH2CH2CO2H


303.
OCH3
H
OCH2C6H5
CH2CH═CHCO2H


304.
OCH3
H
OCH2C6H5
CH2CH═CHCO2H


305.
OCH3
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


306.
OCH3
H
OCH2C6H5
CH2CH2P—O(OH)2


307.
OCH2CH═CH2
H
OCH2C6H5
CO2CH2CH3


308.
OCH2CH═CH2
H
OCH2C6H5
CO2H


309.
OCH2CH═CH2
H
OCH2C6H5
CH2CO2CH2CH3


310.
OCH2CH═CH2
H
OCH2C6H5
CH2CO2H


311.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2CO2CH2CH3


312.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2CO2H


313.
OCH2CH═CH2
H
OCH2C6H5
CH2CH═CHCO2H


314.
OCH2CH═CH2
H
OCH2C6H5
CH2CH═CHCO2H


315.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


316.
OCH2CH═CH2
H
OCH2C6H5
CH2CH2P—O(OH)2


317.
OCH2C6H5
H
OCH2C6H5
CO2CH2CH3


318.
OCH2C6H5
H
OCH2C6H5
CO2H


319.
OCH2C6H5
H
OCH2C6H5
CH2CO2CH2CH3


320.
OCH2C6H5
H
OCH2C6H5
CH2CO2H


321.
OCH2C6H5
H
OCH2C6H5
CH2CH2CO2CH2CH3


322.
OCH2C6H5
H
OCH2C6H5
CH2CH2CO2H


323.
OCH2C6H5
H
OCH2C6H5
CH2CH═CHCO2H


324.
OCH2C6H5
H
OCH2C6H5
CH2CH═CHCO2H


325.
OCH2C6H5
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


326.
OCH2C6H5
H
OCH2C6H5
CH2CH2P—O(OH)2


327.
Cl
H
OCH2C6H5
CO2CH2CH3


328.
Cl
H
OCH2C6H5
CO2H


329.
Cl
H
OCH2C6H5
CH2CO2CH2CH3


330.
Cl
H
OCH2C6H5
CH2CO2H


331.
Cl
H
OCH2C6H5
CH2CH2CO2CH2CH3


332.
Cl
H
OCH2C6H5
CH2CH2CO2H


333.
Cl
H
OCH2C6H5
CH2CH═CHCO2H


334.
Cl
H
OCH2C6H5
CH2CH═CHCO2H


335.
Cl
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


336.
Cl
H
OCH2C6H5
CH2CH2P—O(OH)2


337.
NO2
H
OCH2C6H5
CO2CH2CH3


338.
NO2
H
OCH2C6H5
CO2H


339.
NO2
H
OCH2C6H5
CH2CO2CH2CH3


340.
NO2
H
OCH2C6H5
CH2CO2H


341.
NO2
H
OCH2C6H5
CH2CH2CO2CH2CH3


342.
NO2
H
OCH2C6H5
CH2CH2CO2H


343.
NO2
H
OCH2C6H5
CH2CH═CHCO2H


344.
NO2
H
OCH2C6H5
CH2CH═CHCO2H


345.
NO2
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


346.
NO2
H
OCH2C6H5
CH2CH2P—O(OH)2


347.
NHSO2CH3 
H
OCH2C6H5
H


348.
NHSO2CH3
H
OCH2C6H5
CH3


349.
NHSO2CH3
H
OCH2C6H5
CO2CH2CH3


350.
NHSO2CH3
H
OCH2C6H5
CO2H


351.
NHSO2CH3
H
OCH2C6H5
CH2CO2CH2CH3


352.
NHSO2CH3
H
OCH2C6H5
CH2CO2H


353.
NHSO2CH3
H
OCH2C6H5
CH2CH2CO2CH2CH3


354.
NHSO2CH3
H
OCH2C6H5
CH2CH2CO2H


355.
NHSO2CH3
H
OCH2C6H5
CH2CH═CHCO2H


356.
NHSO2CH3
H
OCH2C6H5
CH2CH═CHCO2H


357.
NHSO2CH3
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


358.
NHSO2CH3
H
OCH2C6H5
CH2CH2P—O(OH)2


359.
OCH2CONH2
H
OCH2C6H5
H


360.
OCH2CONH2
H
OCH2C6H5
CH3


361.
OCH2CONH2
H
OCH2C6H5
CO2CH2CH3


362.
OCH2CONH2
H
OCH2C6H5
CO2H


363.
OCH2CONH2
H
OCH2C6H5
CH2CO2CH2CH3


364.
OCH2CONH2
H
OCH2C6H5
CH2CO2H


365.
OCH2CONH2
H
OCH2C6H5
CH2CH2CO2CH2CH3


366.
OCH2CONH2
H
OCH2C6H5
CH2CH2CO2H


367.
OCH2CONH2
H
OCH2C6H5
CH2CH═CHCO2H


368.
OCH2CONH2
H
OCH2C6H5
CH2CH═CHCO2H


369.
OCH2CONH2
H
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


370.
OCH2CONH2
H
OCH2C6H5
CH2CH2P—O(OH)2


371.
OH
CH2N(CH3)2
OCH2C6H5
CO2CH2CH3


372.
OH
CH2N(CH3)2
OCH2C6H5
CO2H


373.
OH
CH2N(CH3)2
OCH2C6H5
CH2CO2CH2CH3


374.
OH
CH2N(CH3)2
OCH2C6H5
CH2CO2H


375.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2CH2CH3


376.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2H


377.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


378.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


379.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


380.
OH
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OH)2


381.
OCH3
CH2N(CH3)2
OCH2C6H5
CO2CH2CH3


382.
OCH3
CH2N(CH3)2
OCH2C6H5
CO2H


383.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CO2CH2CH3


384.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CO2H


385.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2CH2CH3


386.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2CO2H


387.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


388.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH═CHCO2H


389.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OCH2CH3)2


390.
OCH3
CH2N(CH3)2
OCH2C6H5
CH2CH2P—O(OH)2


391.
OH
CH2N+(CH3)3 
OCH2C6H5
H




Cl−




392.
OH
CH2N+(CH3)3 
OCH2C6H5
CH3




Cl−




393.
OH
CH2N+(CH3)3 
OCH2C6H5
CO2CH2CH3




Cl−




394.
OH
CH2N+(CH3)3 
OCH2C6H5
CO2H




Cl−




395.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CO2CH2CH3




Cl−




396.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CO2H




Cl−




397.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH2CO2CH2CH3




Cl−




398.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH2CO2H




Cl−




399.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH═CHCO2H




Cl−




400.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH═CHCO2H




Cl−




401.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH2P—O(OCH2CH3)2




Cl−




402.
OH
CH2N+(CH3)3 
OCH2C6H5
CH2CH2P—O(OH)2




Cl−




403.
OCH3
CH2N+(CH3)3 
OCH2C6H5
H




Cl−




404.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH3




Cl−




405.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CO2CH2CH3




Cl−




406.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CO2H




Cl−




407.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CO2CH2CH3




Cl−




408.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CO2H




Cl−




409.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH2CO2CH2CH3




Cl−




410.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH2CO2H




Cl−




411.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH═CHCO2H




Cl−




412.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH═CHCO2H




Cl−




413.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH2P—O(OCH2CH3)2




Cl−




414.
OCH3
CH2N+(CH3)3 
OCH2C6H5
CH2CH2P—O(OH)2




Cl−




415.
H
H
OCH2CH═CH2
CO2CH2CH3


416.
H
H
OCH2CH═CH2
CO2H


417.
H
H
OCH2CH═CH2
CH2CO2CH2CH3


418.
H
H
OCH2CH═CH2
CH2CO2H


419.
H
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


420.
H
H
OCH2CH═CH2
CH2CH2CO2H


421.
H
H
OCH2CH═CH2
CH2CH═CHCO2H


422.
H
H
OCH2CH═CH2
CH2CH═CHCO2H


423.
H
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


424.
H
H
OCH2CH═CH2
CH2CH2P—O(OH)2


425.
OH
H
OCH2CH═CH2
CO2CH2CH3


426.
OH
H
OCH2CH═CH2
CO2H


427.
OH
H
OCH2CH═CH2
CH2CO2CH2CH3


428.
OH
H
OCH2CH═CH2
CH2CO2H


429.
OH
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


430.
OH
H
OCH2CH═CH2
CH2CH2CO2H


431.
OH
H
OCH2CH═CH2
CH2CH═CHCO2H


432.
OH
H
OCH2CH═CH2
CH2CH═CHCO2H


433.
OH
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


434.
OH
H
OCH2CH═CH2
CH2CH2P—O(OH)2


435.
OCH3
H
OCH2CH═CH2
CO2CH2CH3


436.
OCH3
H
OCH2CH═CH2
CO2H


437.
OCH3
H
OCH2CH═CH2
CH2CO2CH2CH3


438.
OCH3
H
OCH2CH═CH2
CH2CO2H


439.
OCH3
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


440.
OCH3
H
OCH2CH═CH2
CH2CH2CO2H


441.
OCH3
H
OCH2CH═CH2
CH2CH═CHCO2H


442.
OCH3
H
OCH2CH═CH2
CH2CH═CHCO2H


443.
OCH3
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


444.
OCH3
H
OCH2CH═CH2
CH2CH2P—O(OH)2


445.
OCH2CH═CH2
H
OCH2CH═CH2
CO2CH2CH3


446.
OCH2CH═CH2
H
OCH2CH═CH2
CO2H


447.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CO2CH2CH3


448.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CO2H


449.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


450.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2CO2H


451.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH═CHCO2H


452.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH═CHCO2H


453.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


454.
OCH2CH═CH2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


455.
OCH2C6H5
H
OCH2CH═CH2
CO2CH2CH3


456.
OCH2C6H5
H
OCH2CH═CH2
CO2H


457.
OCH2C6H5
H
OCH2CH═CH2
CH2CO2CH2CH3


458.
OCH2C6H5
H
OCH2CH═CH2
CH2CO2H


459.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


460.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2CO2H


461.
OCH2C6H5
H
OCH2CH═CH2
CH2CH═CHCO2H


462.
OCH2C6H5
H
OCH2CH═CH2
CH2CH═CHCO2H


463.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


464.
OCH2C6H5
H
OCH2CH═CH2
CH2CH2P—O(OH)2


465.
Cl
H
OCH2CH═CH2
CO2CH2CH3


466.
Cl
H
OCH2CH═CH2
CO2H


467.
Cl
H
OCH2CH═CH2
CH2CO2CH2CH3


468.
Cl
H
OCH2CH═CH2
CH2CO2H


469.
Cl
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


470.
Cl
H
OCH2CH═CH2
CH2CH2CO2H


471.
Cl
H
OCH2CH═CH2
CH2CH═CHCO2H


472.
Cl
H
OCH2CH═CH2
CH2CH═CHCO2H


473.
Cl
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


474.
Cl
H
OCH2CH═CH2
CH2CH2P—O(OH)2


475.
NO2
H
OCH2CH═CH2
CO2CH2CH3


476.
NO2
H
OCH2CH═CH2
CO2H


477.
NO2
H
OCH2CH═CH2
CH2CO2CH2CH3


478.
NO2
H
OCH2CH═CH2
CH2CO2H


479.
NO2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


480.
NO2
H
OCH2CH═CH2
CH2CH2CO2H


481.
NO2
H
OCH2CH═CH2
CH2CH═CHCO2H


482.
NO2
H
OCH2CH═CH2
CH2CH═CHCO2H


483.
NO2
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


484.
NO2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


485.
NHSO2CH3
H
OCH2CH═CH2
H


486.
NHSO2CH3
H
OCH2CH═CH2
CH3


487.
NHSO2CH3
H
OCH2CH═CH2
CO2CH2CH3


488.
NHSO2CH3
H
OCH2CH═CH2
CO2H


489.
NHSO2CH3
H
OCH2CH═CH2
CH2CO2CH2CH3


490.
NHSO2CH3
H
OCH2CH═CH2
CH2CO2H


491.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


492.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2CO2H


493.
NHSO2CH3
H
OCH2CH═CH2
CH2CH═CHCO2H


494.
NHSO2CH3
H
OCH2CH═CH2
CH2CH═CHCO2H


495.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


496.
NHSO2CH3
H
OCH2CH═CH2
CH2CH2P—O(OH)2


497.
OCH2CONH2
H
OCH2CH═CH2
H


498.
OCH2CONH2
H
OCH2CH═CH2
CH3


499.
OCH2CONH2
H
OCH2CH═CH2
CO2CH2CH3


500.
OCH2CONH2
H
OCH2CH═CH2
CO2H


501.
OCH2CONH2
H
OCH2CH═CH2
CH2CO2CH2CH3


502.
OCH2CONH2
H
OCH2CH═CH2
CH2CO2H


503.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2CO2CH2CH3


504.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2CO2H


505.
OCH2CONH2
H
OCH2CH═CH2
CH2CH═CHCO2H


506.
OCH2CONH2
H
OCH2CH═CH2
CH2CH═CHCO2H


507.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


508.
OCH2CONH2
H
OCH2CH═CH2
CH2CH2P—O(OH)2


509.
OH
CH2N(CH3)2
OCH2CH═CH2
CO2CH2CH3


510.
OH
CH2N(CH3)2
OCH2CH═CH2
CO2H


511.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CO2CH2CH3


512.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CO2H


513.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2CH2CH3


514.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2H


515.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


516.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


517.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


518.
OH
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OH)2


519.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CO2CH2CH3


520.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CO2H


521.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CO2CH2CH3


522.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CO2H


523.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2CH2CH3


524.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2CO2H


525.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


526.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH═CHCO2H


527.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2


528.
OCH3
CH2N(CH3)2
OCH2CH═CH2
CH2CH2P—O(OH)2


529.
OH
CH2N+(CH3)3 
OCH2CH═CH2
H




Cl−




530.
OH
CH2N+(CH3)3 
OCH2CH═CH2
CH3




Cl−




531.
OH
CH2N+(CH3)3 
OCH2CH═CH2
CO2CH2CH3




Cl−




532.
OH
CH2N+(CH3)3
OCH2CH═CH2
CO2H




Cl−




533.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2CH2CH3




Cl−




534.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2H




Cl−




535.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2CH2CH3




Cl−




536.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2H




Cl−




537.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




538.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




539.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—O( OCH2CH3)2




Cl−




540.
OH
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2P—O(OH)2




Cl−




541.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
H




Cl−




542.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH3




Cl−




543.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CO2CH2CH3




Cl−




544.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CO2H




Cl−




545.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CO2CH2CH3




Cl−




546.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CO2H




Cl−




547.
OCH3
CH2N+(CH3)3
OCH2CH═CH2
CH2CH2CO2CH2CH3




Cl−




548.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CH2CO2H




Cl−




549.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




550.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CH═CHCO2H




Cl−




551.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CH2P—O(OCH2CH3)2




Cl−




552.
OCH3
CH2N+(CH3)3 
OCH2CH═CH2
CH2CH2P—O(OH)2




Cl−




553.
H
H
OCH2CONH2
H


554.
H
H
OCH2CONH2
CH3


555.
H
H
OCH2CONH2
CO2CH2CH3


556.
H
H
OCH2CONH2
CO2H


557.
H
H
OCH2CONH2
CH2CO2CH2CH3


558.
H
H
OCH2CONH2
CH2CO2H


559.
H
H
OCH2CONH2
CH2CH2CO2CH2CH3


560.
H
H
OCH2CONH2
CH2CH2CO2H


561.
H
H
OCH2CONH2
CH2CH═CHCO2H


562.
H
H
OCH2CONH2
CH2CH═CHCO2H


563.
H
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


564.
H
H
OCH2CONH2
CH2CH2P—O(OH)2


565.
OH
H
OCH2CONH2
H


566.
OH
H
OCH2CONH2
CH3


567.
OH
H
OCH2CONH2
CO2CH2CH3


568.
OH
H
OCH2CONH2
CO2H


569.
OH
H
OCH2CONH2
CH2CO2CH2CH3


570.
OH
H
OCH2CONH2
CH2CO2H


571.
OH
H
OCH2CONH2
CH2CH2CO2CH2CH3


572.
OH
H
OCH2CONH2
CH2CH2CO2H


573.
OH
H
OCH2CONH2
CH2CH═CHCO2H


574.
OH
H
OCH2CONH2
CH2CH═CHCO2H


575.
OH
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


576.
OH
H
OCH2CONH2
CH2CH2P—O(OH)2


577.
OCH3
H
OCH2CONH2
H


578.
OCH3
H
OCH2CONH2
CH3


579.
OCH3
H
OCH2CONH2
CO2CH2CH3


580.
OCH3
H
OCH2CONH2
CO2H


581.
OCH3
H
OCH2CONH2
CH2CO2CH2CH3


582.
OCH3
H
OCH2CONH2
CH2CO2H


583.
OCH3
H
OCH2CONH2
CH2CH2CO2CH2CH3


584.
OCH3
H
OCH2CONH2
CH2CH2CO2H


585.
OCH3
H
OCH2CONH2
CH2CH═CHCO2H


586.
OCH3
H
OCH2CONH2
CH2CH═CHCO2H


587.
OCH3
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


588.
OCH3
H
OCH2CONH2
CH2CH2P—O(OH)2


589.
OCH2CH═CH2
H
OCH2CONH2
H


590.
OCH2CH═CH2
H
OCH2CONH2
CH3


591.
OCH2CH═CH2
H
OCH2CONH2
CO2CH2CH3


592.
OCH2CH═CH2
H
OCH2CONH2
CO2H


593.
OCH2CH═CH2
H
OCH2CONH2
CH2CO2CH2CH3


594.
OCH2CH═CH2
H
OCH2CONH2
CH2CO2H


595.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2CO2CH2CH3


596.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2CO2H


597.
OCH2CH═CH2
H
OCH2CONH2
CH2CH═CHCO2H


598.
OCH2CH═CH2
H
OCH2CONH2
CH2CH═CHCO2H


599.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


600.
OCH2CH═CH2
H
OCH2CONH2
CH2CH2P—O(OH)2


601.
OCH2C6H5
H
OCH2CONH2
H


602.
OCH2C6H5
H
OCH2CONH2
CH3


603.
OCH2C6H5
H
OCH2CONH2
CO2CH2CH3


604.
OCH2C6H5
H
OCH2CONH2
CO2H


605.
OCH2C6H5
H
OCH2CONH2
CH2CO2CH2CH3


606.
OCH2C6H5
H
OCH2CONH2
CH2CO2H


607.
OCH2C6H5
H
OCH2CONH2
CH2CH2CO2CH2CH3


608.
OCH2C6H5
H
OCH2CONH2
CH2CH2CO2H


609.
OCH2C6H5
H
OCH2CONH2
CH2CH═CHCO2H


610.
OCH2C6H5
H
OCH2CONH2
CH2CH═CHCO2H


611.
OCH2C6H5
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


612.
OCH2C6H5
H
OCH2CONH2
CH2CH2P—O(OH)2


613.
Cl
H
OCH2CONH2
H


614.
Cl
H
OCH2CONH2
CH3


615.
Cl
H
OCH2CONH2
CO2CH2CH3


616.
Cl
H
OCH2CONH2
CO2H


617.
Cl
H
OCH2CONH2
CH2CO2CH2CH3


618.
Cl
H
OCH2CONH2
CH2CO2H


619.
Cl
H
OCH2CONH2
CH2CH2CO2CH2CH3


620.
Cl
H
OCH2CONH2
CH2CH2CO2H


621.
Cl
H
OCH2CONH2
CH2CH═CHCO2H


622.
Cl
H
OCH2CONH2
CH2CH═CHCO2H


623.
Cl
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


624.
Cl
H
OCH2CONH2
CH2CH2P—O(OH)2


625.
NO2
H
OCH2CONH2
H


626.
NO2
H
OCH2CONH2
CH3


627.
NO2
H
OCH2CONH2
CO2CH2CH3


628.
NO2
H
OCH2CONH2
CO2H


629.
NO2
H
OCH2CONH2
CH2CO2CH2CH3


630.
NO2
H
OCH2CONH2
CH2CO2H


631.
NO2
H
OCH2CONH2
CH2CH2CO2CH2CH3


632.
NO2
H
OCH2CONH2
CH2CH2CO2H


633.
NO2
H
OCH2CONH2
CH2CH═CHCO2H


634.
NO2
H
OCH2CONH2
CH2CH═CHCO2H


635.
NO2
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


636.
NO2
H
OCH2CONH2
CH2CH2P—O(OH)2


637.
NHSO2CH3
H
OCH2CONH2
H


638.
NHSO2CH3
H
OCH2CONH2
CH3


639.
NHSO2CH3
H
OCH2CONH2
CO2CH2CH3


640.
NHSO2CH3
H
OCH2CONH2
CO2H


641.
NHSO2CH3
H
OCH2CONH2
CH2CO2CH2CH3


642.
NHSO2CH3
H
OCH2CONH2
CH2CO2H


643.
NHSO2CH3
H
OCH2CONH2
CH2CH2CO2CH2CH3


644.
NHSO2CH3
H
OCH2CONH2
CH2CH2CO2H


645.
NHSO2CH3
H
OCH2CONH2
CH2CH═CHCO2H


646.
NHSO2CH3
H
OCH2CONH2
CH2CH═CHCO2H


647.
NHSO2CH3
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


648.
NHSO2CH3
H
OCH2CONH2
CH2CH2P—O(OH)2


649.
OCH2CONH2 
H
OCH2CONH2
H


650.
OCH2CONH2 
H
OCH2CONH2
CH3


651.
OCH2CONH2 
H
OCH2CONH2
CO2CH2CH3


652.
OCH2CONH2 
H
OCH2CONH2
CO2H


653.
OCH2CONH2 
H
OCH2CONH2
CH2CO2CH2CH3


654.
OCH2CONH2 
H
OCH2CONH2
CH2CO2H


655.
OCH2CONH2 
H
OCH2CONH2
CH2CH2CO2CH2CH3


656.
OCH2CONH2 
H
OCH2CONH2
CH2CH2CO2H


657.
OCH2CONH2 
H
OCH2CONH2
CH2CH═CHCO2H


658.
OCH2CONH2 
H
OCH2CONH2
CH2CH═CHCO2H


659.
OCH2CONH2 
H
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


660.
OCH2CONH2 
H
OCH2CONH2
CH2CH2P—O(OH)2


661.
OH
CH2N(CH3)2
OCH2CONH2
H


662.
OH
CH2N(CH3)2
OCH2CONH2
CH3


663.
OH
CH2N(CH3)2
OCH2CONH2
CO2CH2CH3


664.
OH
CH2N(CH3)2
OCH2CONH2
CO2H


665.
OH
CH2N(CH3)2
OCH2CONH2
CH2CO2CH2CH3


666.
OH
CH2N(CH3)2
OCH2CONH2
CH2CO2H


667.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2CH2CH3


668.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2H


669.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


670.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


671.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


672.
OH
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OH)2


673.
OCH3
CH2N(CH3)2
OCH2CONH2
H


674.
OCH3
CH2N(CH3)2
OCH2CONH2
CH3


675.
OCH3
CH2N(CH3)2
OCH2CONH2
CO2CH2CH3


676.
OCH3
CH2N(CH3)2
OCH2CONH2
CO2H


677.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CO2CH2CH3


678.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CO2H


679.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2CH2CH3


680.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2CO2H


681.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


682.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH═CHCO2H


683.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OCH2CH3)2


684.
OCH3
CH2N(CH3)2
OCH2CONH2
CH2CH2P—O(OH)2


685.
OH
CH2N+(CH3)3
OCH2CONH2
H




Cl−




686.
OH
CH2N+(CH3)3
OCH2CONH2
CH3




Cl−




687.
OH
CH2N+(CH3)3
OCH2CONH2
CO2CH2CH3




Cl−




688.
OH
CH2N+(CH3)3
OCH2CONH2
CO2H




Cl−




689.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CO2CH2CH3




Cl−




690.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CO2H




Cl−




691.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2CH2CH3




Cl−




692.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2H




Cl−




693.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




694.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH═CHCO2H




Cl−




695.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—O(OCH2CH3)2




Cl−




696.
OH
CH2N+(CH3)3
OCH2CONH2
CH2CH2P—O(OH)2




Cl−




697.
OCH3
CH2N+(CH3)3 
OCH2CONH2
H




Cl−




698.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH3




Cl−




699.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CO2CH2CH3




Cl−




700.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CO2H




Cl−




701.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CO2CH2CH3




Cl−




702.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CO2H




Cl−




703.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2CH2CH3




Cl−




704.
OCH3
CH2N+(CH3)3
OCH2CONH2
CH2CH2CO2H




Cl−




705.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CH═CHCO2H




Cl−




706.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CH═CHCO2H




Cl−




707.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CH2P—O( OCH2CH3)2




Cl−




708.
OCH3
CH2N+(CH3)3 
OCH2CONH2
CH2CH2P—O(OH)2




Cl−
















TABLE VIIIa













 









Ex. #
X
R1












3.
CN
H


4.
CN
CH3


5.
CONH2
H


6.
CONH2
CH3


7.
CO2H
H


8.
CO2H
CH3


9.
NHSO2CH3
H


10.
NHSO2CH3
CH3


11.
OCH2C6H5
H


12.
OCH2C6H5
CH3


13.
OCH2C6H4C6H5
H


14.
OCH2C6H4C6H5
CH3


15.
OCH2CH2C6H5
H


16.
OCH2CH2C6H5
CH3


17.
OCH2C6H4Cl (2, 3, or 4)
H


18.
OCH2C6H4Cl (2, 3, or 4)
CH3


19.
OCH2C6H4OCH3 (2, 3, or 4)
H


20.
OCH2C6H4OCH3 (2, 3, or 4)
CH3


21.
OCH2C6H4F (2, 3, or 4)
H


22.
OCH2C6H4F (2, 3, or 4)
CH3


23.
OCH2C6H4CN (2, 3, or 4)
H


24.
OCH2C6H4CN (2, 3, or 4)
CH3


25.
OCH2C6H4CONH2 (2, 3, or 4)
H


26.
OCH2C6H4CONH2 (2, 3, or 4)
CH3


27.
OCH2C6H4CH2CN (2, 3, or 4)
H


28.
OCH2C6H4CH2CN (2, 3, or 4)
CH3


29.
OCH2C6H4CH2CONH2 (2, 3, or 4)
H


30.
OCH2C6H4CH2CONH2 (2, 3, or 4)
CH3


31.
OCH2C6H4OCH2CN (2, 3, or 4)
H


32.
OCH2C6H4OCH2CN (2, 3, or 4)
CH3


33.
OCH2C6H4OCH2CONH2 (2, 3, or 4)
H


34.
OCH2C6H4OCH2CONH2 (2, 3, or 4)
CH3


35.
OCH2C6H3(CN)2 (3, 5)
H


36.
OCH2C6H3(CN)2 (3, 5)
CH3


37.
OCH2C6H3(CONH2)2 (3, 5)
H


38.
OCH2C6H3(CONH2)2 (3, 5)
CH3


39.
OCH2C6H4—NO2 (2, 3, or 4)
H


40.
OCH2C6H4—NO2 (2, 3, or 4)
CH3


41.
OCH2C6H4—CF3 (2, 3, or 4)
H


42.
OCH2C6H4—CF3 (2, 3, or 4)
CH3


43.
OCH2C6H4—CH3 (2, 3, or 4)
H


44.
OCH2C6H4—CH3 (2, 3, or 4)
CH3


45.
OCH2C6H4—NHSO2CH3 (2, 3, or 4)
H


46.
OCH2C6H4—NHSO2CH3 (2, 3, or 4)
CH3


47.
OCH2C6H4C6H4CN (2, 3, or 4)
H


48.
OCH2C6H4C6H4CN (2, 3, or 4)
CH3


49.
OCH2C6H4C6H4CONH2 (2, 3, or 4)
H


50.
OCH2C6H4C6H4CONH2 (2, 3, or 4)
CH3


51.
OCH2C6H4C6H4CO2H (2, 3, or 4)
H


52.
OCH2C6H4C6H4CO2H (2, 3, or 4)
CH3
















TABLE VIIIb













 









Ex. #
X′
R1












1.
CN
H


2.
CN
CH3


3.
CONH2
H


4.
CONH2
CH3


5.
CO2H
H


6.
CO2H
CH3


7.
NHSO2CH3
H


8.
NHSO2CH3
CH3


9.
OCH2C6H5
H


10.
OCH2C6H5
CH3


11.
OCH2CH2C6H5
H


12.
OCH2C6H4C6H5
H


13.
OCH2C6H4C6H5
CH3


14.
OCH2CH2C6H5
CH3


15.
OCH2C6H4—Cl (2, 3, or 4)
H


16.
OCH2C6H4—Cl (2, 3, or 4)
CH3


17.
OCH2C6H4—OCH3 (2, 3, or 4)
H


18.
OCH2C6H4—OCH3 (2, 3, or 4)
CH3


19.
OCH2C6H4—F (2, 3, or 4)
H


20.
OCH2C6H4—F (2, 3, or 4)
CH3


21.
OCH2C6H4CN (2, 3, or 4)
H


22.
OCH2C6H4CN (2, 3, or 4)
CH3


23.
OCH2C6H4CONH2 (2, 3, or 4)
H


24.
OCH2C6H4CONH2 (2, 3, or 4)
CH3


25.
OCH2C6H4CH2CN (2, 3, or 4)
H


26.
OCH2C6H4CH2CN (2, 3, or 4)
CH3


27.
OCH2C6H4CH2CONH2 (2, 3, or 4)
H


28.
OCH2C6H4CH2CONH2 (2, 3, or 4)
CH3


29.
OCH2C6H4OCH2CN (2, 3, or 4)
H


30.
OCH2C6H4OCH2CN (2, 3, or 4)
CH3


31.
OCH2C6H4OCH2CONH2 (2, 3, or 4)
H


32.
OCH2C6H4OCH2CONH2 (2, 3, or 4)
CH3


33.
OCH2C6H3(CN)2 (3, 5)
H


34.
OCH2C6H3(CN)2 (3, 5)
CH3


35.
OCH2C6H3(CONH2)2 (3, 5)
H


36.
OCH2C6H3(CONH2)2 (3, 5)
CH3


37.
OCH2C6H4—NO2(2, 3, or 4)
H


38.
OCH2C6H4—NO2(2, 3, or 4)
CH3


39.
OCH2C6H4—CF3 (2, 3, or 4)
H


40.
OCH2C6H4—CF3 (2, 3, or 4)
CH3


41.
OCH2C6H4—CH3 (2, 3, or 4)
H


42.
OCH2C6H4—CH3 (2, 3, or 4)
CH3


43.
OCH2C6H4—NHSO2CH3 (2, 3, or 4)
H


44.
OCH2C6H4—NHSO2CH3 (2, 3, or 4)
CH3


45.
OCH2C6H4C6H4CN (2, 3, or 4)
H


46.
OCH2C6H4C6H4CN (2, 3, or 4)
CH3


47.
OCH2C6H4C6H4CONH2 (2, 3, or 4)
H


48.
OCH2C6H4C6H4CONH2 (2, 3, or 4)
CH3


49.
OCH2C6H4C6H4CO2H (2, 3, or 4)
H


50.
OCH2C6H4C6H4CO2H (2, 3, or 4)
CH3
















TABLEVIIIc













 











Ex. #
X
R1















1.
NHCH2C6H5
H



2.
NHCH2C6H5
CH3



3.
NHCH2C6H4C6H5
H



4.
NHCH2C6H4C6H5
CH3



5.
NHCH2CH2C6H5
H



6.
NHCH2CH2C6H5
CH3



7.
NHCH2C6H4—Cl (2, 3, or 4)
H



8.
NHCH2C6H4—Cl (2, 3, or 4)
CH3



9.
NHCH2C6H4—OCH3 (2, 3, or 4)
H



10.
NHCH2C6H4—OCH3 (2, 3, or 4)
CH3



11.
NHCH2C6H4—F (2, 3, or 4)
H



12.
NHCH2C6H4—F (2, 3, or 4)
CH3



13.
NHCH2C6H4CN (2, 3, or 4)
H



14.
NHCH2C6H4CN (2, 3, or 4)
CH3



15.
NHCH2C6H4CONH2 (2, 3, or 4)
H



16.
NHCH2C6H4CONH2 (2, 3, or 4)
CH3



17.
NHCH2C6H4CH2CN (2, 3, or 4)
H



18.
NHCH2C6H4CH2CN (2, 3, or 4)
CH3



19.
NHCH2C6H4CH2CONH2 (2, 3, or 4)
H



20.
NHCH2C6H4CH2CONH2 (2, 3, or 4)
CH3



21.
NHCH2C6H4OCH2CN (2, 3, or 4)
H



22.
NHCH2C6H4OCH2CN (2, 3, or 4)
CH3



23.
NHCH2C6H4OCH2CONH2 (2, 3, or 4)
H



24.
NHCH2C6H4OCH2CONH2 (2, 3, or 4)
CH3



25.
NHCH2C6H3(CN)2 (3, 5)
H



26.
NHCH2C6H3(CN)2 (3, 5)
CH3



27.
NHCH2C6H3(CONH2)2 (3, 5)
H



28.
NHCH2C6H3(CONH2)2 (3, 5)
CH3



29.
NHCH2C6H4—NO2 (2, 3, or 4)
H



30.
NHCH2C6H4—NO2 (2, 3, or 4)
CH3



31.
NHCH2C6H4—CF3 (2, 3, or 4)
H



32.
NHCH2C6H4—CF3 (2, 3, or 4)
CH3



33.
NHCH2C6H4—CH3 (2, 3, or 4)
H



34.
NHCH2C6H4—CH3 (2, 3, or 4)
CH3



35.
NHCH2C6H4—NHSO2CH3 (2, 3, or 4)
H



36.
NHCH2C6H4—NHSO2CH3 (2, 3, or 4)
CH3



37.
NHCH2C6H4C6H4CN (2, 3, or 4)
H



38.
NHCH2C6H4C6H4CN (2, 3, or 4)
CH3



39.
NHCH2C6H4C6H4CONH2 (2, 3, or 4)
H



40.
NHCH2C6H4C6H4CONH2 (2, 3, or 4)
CH3



41.
NHCH2C6H4C6H4CO2H (2, 3, or 4)
H



42.
NHCH2C6H4C6H4CO2H (2, 3, or 4)
CH3

















TABLE VIIId


























1.
NHCH2C6H5
H


2.
NHCH2C6H5
CH3


3.
NHCH2C6H4C6H5
H


4.
NHCH2C6H4C6H5
CH3


5.
NHCH2CH2C6H5
H


6.
NHCH2CH2C6H5
CH3


7.
NHCH2C6H4—Cl (2, 3, or 4)
H


8.
NHCH2C6H4—Cl (2, 3, or 4)
CH3


9.
NHCH2C6H4—OCH3 (2, 3, or 4)
H


10.
NHCH2C6H4—OCH3 (2, 3, or 4)
CH3


11.
NHCH2C6H4—F (2, 3, or 4)
H


12.
NHCH2C6H4—F (2, 3, or 4)
CH3


13.
NHCH2C6H4CN (2, 3, or 4)
H


14.
NHCH2C6H4CN (2, 3, or 4)
CH3


15.
NHCH2C6H4CONH2 (2, 3, or 4)
H


16.
NHCH2C6H4CONH2 (2, 3, or 4)
CH3


17.
NHCH2C6H4CH2CN (2, 3, or 4)
H


18.
NHCH2C6H4CH2CN (2, 3, or 4)
CH3


19.
NHCH2C6H4CH2CONH2 (2, 3, or 4)
H


20.
NHCH2C6H4CH2CONH2 (2, 3, or 4)
CH3


21.
NHCH2C6H4OCH2CN (2, 3, or 4)
H


22.
NHCH2C6H4OCH2CN (2, 3, or 4)
CH3


23.
NHCH2C6H4OCH2CONH2 (2, 3, or 4)
H


24.
NHCH2C6H4OCH2CONH2 (2, 3, or 4)
CH3


25.
NHCH2C6H3(CN)2 (3, 5)
H


26.
NHCH2C6H3(CN)2 (3, 5)
CH3


27.
NHCH2C6H3(CONH2)2 (3, 5)
H


28.
NHCH2C6H3(CONH2)2 (3, 5)
CH3


29.
NHCH2C6H4—NO2 (2, 3, or 4)
H


30.
NHCH2C6H4—NO2 (2, 3, or 4)
CH3


31.
NHCH2C6H4—CF3 (2, 3, or 4)
H


32.
NHCH2C6H4—CF3 (2, 3, or 4)
CH3


33.
NHCH2C6H4—CH3 (2, 3, or 4)
H


34.
NHCH2C6H4—CH3 (2, 3, or 4)
CH3


35.
NHCH2C6H4—NHSO2CH3 (2, 3, or 4)
H


36.
NHCH2C6H4—NHSO2CH3 (2, 3, or 4)
CH3


37.
NHCH2C6H4C6H4CN (2, 3, or 4)
H


38.
NHCH2C6H4C6H4CN (2, 3, or 4)
CH3


39.
NHCH2C6H4C6H4CONH2 (2, 3, or 4)
H


40.
NHCH2C6H4C6H4CONH2 (2, 3, or 4)
CH3


41.
NHCH2C6H4C6H4CO2H (2, 3, or 4)
H


42.
NHCH2C6H4C6H4CO2H (2, 3, or 4)
CH3
















TABLE IXa













 









Ex #
X
R1












1.
O(CH2CH2O)2CH2CH2OH
H


2.
O(CH2CH2O)2CH2CH2OH
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
H


6.
O(CH2CH2O)3CH2CH2OH
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
H


10.
O(CH2CH2O)4CH2CH2OH
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
H


14.
O(CH2CH2O)5CH2CH2OH
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
H


18.
O(CH2CH2O)7CH2CH2OH
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
H


22.
O(CH2CH2O)9CH2CH2OH
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3
















TABLE IXb













 









Ex #
X
R1












1.
O(CH2CH2O)2CH2CH2OH
H


2.
O(CH2CH2O)2CH2CH2OH
CH3


3.
O(CH2CH2O)2CH2CH2OCH3
H


4.
O(CH2CH2O)2CH2CH2OCH3
CH3


5.
O(CH2CH2O)3CH2CH2OH
H


6.
O(CH2CH2O)3CH2CH2OH
CH3


7.
O(CH2CH2O)3CH2CH2OCH3
H


8.
O(CH2CH2O)3CH2CH2OCH3
CH3


9.
O(CH2CH2O)4CH2CH2OH
H


10.
O(CH2CH2O)4CH2CH2OH
CH3


11.
O(CH2CH2O)4CH2CH2OCH3
H


12.
O(CH2CH2O)4CH2CH2OCH3
CH3


13.
O(CH2CH2O)5CH2CH2OH
H


14.
O(CH2CH2O)5CH2CH2OH
CH3


15.
O(CH2CH2O)5CH2CH2OCH3
H


16.
O(CH2CH2O)5CH2CH2OCH3
CH3


17.
O(CH2CH2O)7CH2CH2OH
H


18.
O(CH2CH2O)7CH2CH2OH
CH3


19.
O(CH2CH2O)7CH2CH2OCH3
H


20.
O(CH2CH2O)7CH2CH2OCH3
CH3


21.
O(CH2CH2O)9CH2CH2OH
H


22.
O(CH2CH2O)9CH2CH2OH
CH3


23.
O(CH2CH2O)9CH2CH2OCH3
H


24.
O(CH2CH2O)9CH2CH2OCH3
CH3.

3. A pharmaceutical composition, comprising: a compound of claim 1 and a pharmaceutically acceptable carrier.

4. A pharmaceutical composition, comprising: a compound of claim 2 and a pharmaceutically acceptable carrier.

5. A compound of claim 2, wherein the compound is selected from Table I, or a stereoisomer or pharmaceutically acceptable salt thereof.

6. A compound of claim 2, wherein the compound is selected from Table IIa, or a stereoisomer or pharmaceutically acceptable salt thereof.

7. A compound of claim 2, wherein the compound is selected from Table IIb, or a stereoisomer or pharmaceutically acceptable salt thereof.

8. A compound of claim 2, wherein the compound is selected from Table IIIa, or a stereoisomer or pharmaceutically acceptable salt thereof.

9. A compound of claim 2, wherein the compound is selected from Table IIIb, or a stereoisomer or pharmaceutically acceptable salt thereof.

10. A compound of claim 2, wherein the compound is selected from Table IVa, or a stereoisomer or pharmaceutically acceptable salt thereof.

11. A compound of claim 2, wherein the compound is selected from Table IVb, or a stereoisomer or pharmaceutically acceptable salt thereof.

12. A compound of claim 2, wherein the compound is selected from Table IVc, or a stereoisomer or pharmaceutically acceptable salt thereof.

13. A compound of claim 2, wherein the compound is selected from Table IVd, or a stereoisomer or pharmaceutically acceptable salt thereof.

14. A compound of claim 2, wherein the compound is selected from Table V, or a stereoisomer or pharmaceutically acceptable salt thereof.

15. A compound of claim 2, wherein the compound is selected from Table VIIIa, or a stereoisomer or pharmaceutically acceptable salt thereof.

16. A compound of claim 2, wherein the compound is selected from Table VIIIb, or a stereoisomer or pharmaceutically acceptable salt thereof.

17. A compound of claim 2, wherein the compound is selected from Table VIIIc, or a stereoisomer or pharmaceutically acceptable salt thereof.

18. A compound of claim 2, wherein the compound is selected from Table VIIId, or a stereoisomer or pharmaceutically acceptable salt thereof.

19. A compound of claim 2, wherein the compound is selected from Table IXa, or a stereoisomer or pharmaceutically acceptable salt thereof.

20. A compound of claim 2, wherein the compound is selected from Table IXb, or a stereoisomer or pharmaceutically acceptable salt thereof.