IL196253A

IL196253A - Biometric sensor and method of performing a biometric function

Info

Publication number: IL196253A
Application number: IL196253A
Authority: IL
Original assignee: Lumidigm Inc; Todd Doucet
Priority date: 2006-07-19
Filing date: 2008-12-29
Publication date: 2014-11-30
Also published as: CN101529445A; JP2009544106A; IL189797A; KR101433882B1; EP2041697A4; KR101489757B1; KR20090040436A; IL196253A0; WO2008111994A1; JP2009511094A; EP2041697A1; IL189797A0; CN101529445B; KR20080050460A

Description

Aminoindane derivative or salt thereof, pharmaceutical composition comprising the same and uses thereof TECHNICAL FIELD

[0001] The present invention relates to an aminoindane derivative or a salt thereof which is useful as a medicine, especially as an NMDA receptor antagonist, and to an NMDA receptor antagonist comprising the same as an active ingredient. The aminoindane derivative or a salt thereof and the NMDA receptor antagonist comprising the same as an active ingredient, of the present invention, are useful for treating or preventing Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, ischemic apoplexy, pain, and the like.

BACKGROUND ART

[0002] Glutamic acid acts as a neurotransmitter in the central nervous system of mammals, and controls the activity of neurocytes or the release of neurotransmitters via a glutamate receptor existing in synapses. At present, a glutamate receptor is classified into an "ionotropic glutamate receptor" and a "metabotropic glutamate receptor" from many pharmacological and biological studies (Hollmann M. and Heinemann S., Annu. Rev. Neurosci., 17 (1994) 31- 108) . An NMDA (N-methyl-D-aspartate ) receptor is an ion-channel glutamate receptor specifically sensitive to the agonist NMDA (Moriyoshi K. et al., Nature, 354 (1991) 31-37; Meguro H. et al., Nature, 357 (1992) 70-74); and this has high Ca 2+ permeability (lino M. et al., J. Physiol., 424 (1990) 151-165) . The NMDA receptor is expressed with a specific pattern in a central nervous system (Ozawa S. et al., Prog. Neurobiol., 54 (1998) 581-618).

[0003] From many pharmacological and biological studies, it is believed that an NMDA receptor may participate in high-order neurologic functions such as memory and learning (Morris RG. , et al., Nature, 319 (1986) 774-776; Tsien JZ. et al., Cell, 87 (1996) 1327-1338). On the other hand, it is suggested that the acute or chronic NMDA receptor hyperactivity or hypoactivity may participate in various nervous system diseases, for example, ischemic apoplexy, hemorrhagic brain injury, traumatic brain injury, neurodegenerative disorders (e.g., Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis), glaucoma, AIDS encephalopathy, dependence, schizophrenia, depression, mania, stress-related diseases, epilepsy, and pain (Beal MF. , FASEB J., 6 (1992) 3338-3344; Heresco-Levy U. and Javitt DC, Euro. Neuropsychopharmacol . , 8 (1998) 141-152; Hewitt DJ., Clin. J. Pain, 16 (2000) S73-79) . Accordingly, drugs capable of controlling the activity of an NMDA receptor would be extremely useful in clinical application.

[0004] As drugs capable of controlling the activity of an NMDA receptor, a large number of non-competitive NMDA receptor antagonists are reported, but many of them have not been used in clinical application because of their side effects based on the NMDA receptor-antagonizing effect thereof, for example, mental aberration such as hallucination or confusion, and giddiness. Some of already-existing NMDA receptor antagonists, for example, ketamine and dextromethorphan have been tried against pain in clinical application (Fisher K. et al., J. Pain Symptom Manage., 20 (2000) 358-373), but the safety margin in the treatment with them is narrow, and their clinical use is limitative (Eide PK. , et al., Pain, 58 (1994) 347-354).

Memantine is known as a non-competitive NMDA receptor antagonist that has comparatively few side effects (Parsons CG., et al., Neuropharmacol . , 38 (1999) 735-767); and recently, it has been reported that this may be effective for Alzheimer's disease (Reisberg B., et al., N. Engl. J. Med., 348 (2003) 1333-1341). However, the safety margin of memantine as a medicine is still not satisfactory, and an NMDA receptor antagonist having a broader safety margin is desired (Ditzler K. , Arzneimittelforschung, 41 (1991) 773-780; Maier C, et al., Pain, 103 (2003) 277-283; Riederer P., et al., Lancet, 338 (1991) 1022-1023). It is expected that creation of such an NMDA receptor antagonist having a broader safety margin may bring about new clinical usefulness of the NMDA receptor antagonist.

[0005] Patent Document 1 describes a pharmaceutical composition for preventing and treating cerebral ischemia, which comprises an adamantane derivative represented by the following general formula or its pharmaceutically acceptable acid-addition salt: [Chem. 1] (wherein Rx and R2 are the same or different, and each represent hydrogen, a linear or branched alkyl group having 1 to 6 carbon atoms, or the like; R3 and R¾ are the same or different, and each represent hydrogen, an alkyl group having 1 to 6 carbon atoms, or the like; and R 5 represents hydrogen or a linear or branched alkyl group having 1 to 6 carbon atoms. See the official gazette for other symbols in the formula) .

In Patent Document 1, the above-mentioned memantine is described as Test Compound No. 1 (memantine is a compound of the formula wherein Ri, R2 and R3 are hydrogen atoms, and R4 and R5 are methyl) .

[0006] Furthermore, Patent Document 2 describes 1-amino-alkylcyclohexane represented by the following general formula as an NMDA receptor antagonist.

[Chem. 2] {wherein R* is - (CH2) n- (CR6R7) m-NR8R9 n + m = 0, 1 or 2; R1 to R9 are each independently selected from a group consisting of a hydrogen atom and Ci-6 lower alkyl; and at least R1, R4 and R5 are lower alkyl. See the official gazette for other symbols in the formula) .

[0007] Furthermore, the present Applicant reports a cyclic amine derivative represented by the following general formula, as an NMDA receptor antagonist in Patent Document 3.

[Chem. 3] (wherein A represents a 5- to 8-membered cyclic amine optionally having a double bond, optionally having a bridge structure and optionally having substituents of R7 to R11 in the ring, -NH2, -NH (lower alkyl), or -N (lower alkyl)2 ring B represents benzene, thiophene, furan, pyrrole, a 5- to 7-membered cycloalkane, or 5- to 7-membered cycloalkene; X1 represents a bond, a lower alkylene, or -L3-D-L4-; and Y1 represents -OH, -O-lower alkyl, -NH2, or -N3. See the official gazette for other symbols in the formula) .

In addition, Patent Document 4 describes 1-aminoindane represented by the following general formula as a therapeutic agent for Parkinson's disease, and the like.

[0008] 196136/2 (wherein Rx and R2 independently represent hydrogen, hydroxy, alkyl, alkoxy, or the like; R3 represents hydrogen, alkyl, hydroxy, alkoxy, and the like, R4 and R5 independently represent hydrogen, alkyl, aryl, or the like; and n represents 0, 1, or 2) .

[0009] Patent Document 1: JP-A-H02-292214 Patent Document 2: Pamphlet of International Patent Publication WO 99/01416 Patent Document 3: Pamphlet of International Patent Publication WO 2006/033318 Patent Document 4 : Pamphlet of International Patent Publication WO 95/18617 DISCLOSURE OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0010] With the increase in the aging population, occurrence of Alzheimer's disease, cerebrovascular dementia, ischemic apoplexy and the like increases these days, and thus it is earnestly desired in the medical field to create an NMDA receptor antagonist having a broader safety margin, which is effective for treating or preventing such diseases as well as Parkinson's disease, pain, and the like. It is an object of the present invention to provide a novel aminoindane derivative or a salt thereof having an 196136/2 excellent NMDA receptor antagonistic activity and having a broader safety margin, and it is another object to provide a medicine comprising the same.

MEANS FOR SOLVING THE PROBLEMS

[0011] The present inventors have found that a novel aminoindane derivative represented by the following general formula (I) or (la), or a slat thereof, which is characterized in that it has an amino group and R1 (lower alkyl, cycloalkyl, -lower alkylene-aryl, aryl which may be substituted, and the like) on carbon atoms of indane, cyclopenta [b] thiophene, cyclopenta [b] furan, cyclopenta [b] pyridine, or cyclopenta [c] pyridine ring, or 2, 3-dihydro-l-benzofuran, 2, 3-dihydro-l-benzothiophene, indoline ring, or the like, and has R2 and R3 (the same or different, each lower alkyl or aryl) on carbon atoms beside them has an excellent NMDA receptor antagonistic activity and a broad safety margin, and thus have completed the present invention. Specifically, the present invention relates to an aminoindane derivative represented by the following general formula (I) or (la), or a salt thereof (hereinafter this may be referred to as "the compound (I) of the present invention" or "the compound (la) of the present invention"). Further, the present invention also relates to an NMDA receptor antagonist, especially a therapeutic agent or a preventing agent for Alzheimer's disease, cerebrovascular dementia, ischemic apoplexy, pain, etc., that comprises the compound (I) or (la), or a salt thereof of the present invention as an active component. Furthermore, the term "aminoindane derivative" as used in the present invention encompasses a wide range of "aminoindane analogs" having rings other than an indane ring, such as cyclopenta [b] thiophene, cyclopenta [b] furan, cyclopenta [b] pyridine, and cyclopenta [c] pyridine rings as described above, and it shall not be limited.

[0012] The compound (I) or (la) of the present invention is distinguished from the compounds as described in Patent Documents 3 and 4 in that it has an amino group, as well as R1 (lower alkyl, cycloalkyl, -lower alkylene-aryl, aryl which may be substituted, and the like) other than a hydrogen atom on an indane ring, and the like, and has R2 and R3 (which may be the same or different, and each represent lower alkyl or aryl) other than hydrogen atoms on a positions thereof. [1] A compound represented by the following general formula (I) or a salt thereof: (wherein the symbols in the formula (I) have the following meanings, respectively: ring A: a 5- or 6-membered hetero ring, or a benzene ring, X: C (R4) (R5) , 0, S, or N(R12) , R1: lower alkyl, cycloalkyl, -lower alkylene-aryl, aryl which may be substituted, heteroaryl which may be substituted, or lower alkyl substituted with one or more halogens, R2 and R3: the same or different, each lower alkyl, or aryl, R4 and R5: the same or different, each a hydrogen atom, lower alkyl, -0-lower alkyl, -OH, -lower alkylene-OH, or -lower alkylene-O-lower alkyl, R6 to R9: the same or different, each a hydrogen atom, lower alkyl, -0-lower alkyl, a halogen atom, lower alkyl substituted with one or more halogens, OH, CN, lower alkenyl, or a nitrogen-containing heterocyclic group, R10, and R11: the same or different, each a hydrogen atom, or lower alkyl, and R12: a hydrogen atom or lower alkyl, provided that R2 and R3 may be taken together with the adjacent carbon atom to form cycloalkyl) .

[0013] [2] A compound represented by the following general formula (la) or a salt thereof: [Chem. 6] (wherein the symbols in the formula (la) above have the following meanings, respectively: R1: lower alkyl, cycloalkyl, -lower alkylene-aryl, aryl which may be substituted, heteroaryl which may be substituted, or lower alkyl substituted with one or more halogens, R2 and R3: the same or different, each lower alkyl, or aryl, R* and R5: the same or different, each a hydrogen atom, lower alkyl, -O-lower alkyl, -OH, -lower alkylene-OH, or -lower alkylene-O-lower alkyl, R6 to R9: the same or different, each a hydrogen atom, lower alkyl, -O-lower alkyl, a halogen atom, lower alkyl substituted with one or more halogens, OH, CN, lower alkenyl, or a nitrogen-containing heterocyclic group, R10 and R11: the same or different, each a hydrogen atom, or lower alkyl, provided that R2 and R3 may be taken together with the adjacent carbon atom to form cycloalkyl) .

[0014] [3] A compound or a salt thereof as described in [2], wherein R4, R5, R10, and R11 in the formula (la) above are each a hydrogen atom. [4] A compound or a salt thereof as described in [3], wherein R2 and R3 in the formula (la) above are the same as or different from each other, and each are lower alkyl, or cycloalkyl formed in combination with the adjacent carbon atom. [5] A compound or a salt thereof as described in [1], which is selected from 2, 2-dimethyl-l-phenylindan-l-amine, 1- (4-fluorophenyl) -2 , 2-dimethylindan-l-amine, 1- (2-methoxyphenyl)-2,2-dimethylindan-l-amine, l-{3-methoxyphenyl) -2, 2-dimethylindan-l-amine, 1,2,2-trimethylindan-l-amine, 1,2,2, 5-tetramethylindan-l-amine, 1,2,2, 6-tetramethylindan-l-amine, 4-fluoro-l, 2, 2-trimethylindan-l-amine, 5-fluoro-1, 2, 2-trimethylindan-l-amine, 7-fluoro-1, 2, 2-trimethylindan-l-amine, 5-methoxy-1, 2, 2-trimethylindan-l-amine, 6-methoxy-l, 2, 2-trimethylindan-l-amine, 6-isopropoxy-l, 2 , 2-trimethylindan- 196136/2 1-amine, l-ethyl-2, 2-dimethylindan-1 -amine, 1-isopropyl-2 , 2-dimethylindan-l-amine, 1 ' -methyl-1 ' , 3 ' -dihydrospiro [cyclopropan-1, 2 ' -indin] -1 ' -amine, 2,4,5,5-tetramethyl-5, 5-dihyro-4H-cyclopenta [b] thiophen-4-amine .

[0015] [6] A pharmaceutical composition comprising a compound or a salt thereof as described in [1] or [2] . [7] A pharmaceutical composition as described in [6], which is an NMDA receptor antagonist. [8] A pharmaceutical composition as described in [6], which is a therapeutic agent for dementia. [9] A use of a compound or a salt thereof as described in [1] or [2] for preparation of an NMDA receptor antagonist or a therapeutic agent for dementia.

[10] A method for treating dementia, comprising administering a therapeutically effective amount of a compound or a salt thereof as described in [1] or [2] to a patient .

EFFECTS OF THE INVENTION

[0016] The compound of the present invention have an NMDA receptor antagonistic activity, and is thus useful for treating or preventing Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, ischemic apoplexy, pain, and the like. 196136/2 BEST MODE FOR CARRYING OUT THE INVENTION [ 0017 ] Hereinbelow, the present invention is described in detail.

Unless otherwise specifically indicated, the terra "lower" as used in the definition of the general formulae in the present specification means a linear or branched carbon chain having 1 to 6 carbon atoms. Accordingly, "lower alkyl" is preferably linear or branched Ci-e alkyl, and examples thereof include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, and isohexyl. Among these, preferred are alkyls having 1 to 4 carbon atoms; and particularly preferred are methyl and ethyl.

Examples of the "lower alkylene" include methylene, ethylene, propylene, butylene, and also other branched lower alkylene. Preferred are lower alkylene having 1 to 3 carbon atoms; more preferred are methylene and ethylene; and particularly preferred is methylene.

Examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Among these, preferred are a fluorine atom, a chlorine atom, and a bromine atom.

The "lower alkyl substituted with one or more halogens" means any of the hydrogen atoms of the "lower alkyl" as described above that is substituted with one or more "halogen atoms". Particularly preferred is CF3.

The "cycloalkyl" means cycloalkyl having 3 to 8 carbon atoms.

The "R2 and R3 are taken together with the adjacent carbon atom to form cycloalkyl" specifically means that cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl are formed as such. Preferred is cyclopropyl.

Examples of the "lower alkenyl" include vinyl, 1- or 2-propenyl, isopropenyl, 2-methyl-l-propenyl, 2-methyl-2-propenyl, 1-methyl-l-propenyl, and l-methyl-2-propenyl . Preferred is vinyl.

Examples of the "lower alkynyl" preferably include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and l-methyl-2-propynyl .

[0018] The "aryl" means a mono- to tri-cyclic aromatic hydrocarbon ring group having 6 to 14 carbon atoms.

Preferably, examples thereof include phenyl, naphthyl, anthryl, and phenanthryl, and particularly preferred is phenyl .

The "heteroaryl" means a 5- or 6-membered aromatic hetero ring group having 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom, and a sulfur atom.

Preferably, examples thereof include thienyl, furyl, pyrrolyl, thiazolyl, pyridyl, and pyrimidyl, and particularly preferred is thienyl.

As the "-lower alkylene-aryl" , particularly preferred are benzyl and phenethyl.

Examples of the "substituent" of the "aryl which may be substituted" or the "heteroaryl which may be substituted" include lower alkyl, -O-lower alkyl, a halogen atom, OH, CN, CF3, -NH2r -NH(lower alkyl), and -N(lower alkyl) 2, but not limited thereto.

The "nitrogen-containing hetero ring group" means a 3 to 7-membered monocyclic nitrogen-containing hetero ring group comprising 1 to 3 nitrogen atoms. Preferred is a 4 to 6-membered monocyclic saturated hetero ring group, and more preferred are azetidyl, pyrrolidyl, and piperidyl.

The "5- or 6-membered hetero ring" means thiophene, furan, pyridine rings, and the like. Thus, in the present invention, it is taken together with an adjacent cyclopentane ring to form 5, 6-dihydro-5H-cyclopenta [b] thiophene, 5, 6-dihydro-5H-cyclopenta [b] furan, 6, 7-dihydro-5H-cyclopenta [b] yridine, 6, 7-dihydro-5H-cyclopenta [c] pyridine rings, and the like.

Furthermore, "X" means hetero atoms such as 0 and S, or NR12, as well as C(R*)(R5). Here, C(R4){R5) means that carbon atoms have substituents of R4 and R5.

[0019] Further, the compounds of the present invention include mixtures of various isomers such as tautomers and optical isomers, as well as individual isomers isolated from them.

The compounds of the present invention may form acid-addition salts. Depending on the type of the substituent therein, the compounds may form salts with bases.

Specifically, the salts include acid-addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; or acidic amino acids such as aspartic acid and glutamic acid; as well as salts with an inorganic base such as sodium, potassium, magnesium, calcium, and aluminum; an organic base such as methylamine, ethylamine, and ethanolamine; or a basic amino acid such as lysine, ornithine; and ammonium salts.

Further, the compounds of the present invention include hydrates, pharmaceutically acceptable various solvates, and crystalline polymorphic substances.

In addition,' naturally, the compounds of the present invention are not limited to those described in the Examples as described below, and include all the compounds of the above general formula (I) or (la), and their pharmaceutically acceptable salts.

[0020] In addition, the compounds of the present invention include prodrugs that are metabolized in living bodies to give the compounds of the above formula (I) or (la), or compounds to be converted to their salts. Examples of the groups to form prodrugs of the compounds of the present invention include the groups as described in Prog. Med., 5:2157-2161 (1985), and the groups as described in Pharmaceutical Research, Drug Design, Hirokawa Publishing Company (1990), Vol. 7, Molecular Planning, p. 163-198.

[0021] [Production Processes] Taking advantage of the characteristics based on the basic structure or the kind of the substituent therein, the compounds of the present invention may be prepared according to various known production processes. Depending on the kind of the functional group, the functional group in the starting compounds or intermediates may be modified into a suitable protected group, or a group that may be readily converted into a functional group, which may be technically effective in preparing the compounds. After the process, the protective group may be optionally removed, and an intended compound may thus be obtained, if necessary. Examples of the functional group include a hydroxyl group and a carboxyl group. Examples of their protective groups include the protective groups described in Greene & Wuts ' "Protective Groups in Organic Synthesis", 2nd Ed. Depending on the reaction condition, these may be used suitably.

Typical production processes for the compounds (I) of the present invention are described below, but it goes without saying that the compounds (la) of the present invention can also be prepared by the methods.

[0022] (Production Processes) The compound (lb) of the present invention can be prepared by the method represented by the scheme 1. That is, indanone (1), and a Grignard reagent or an organic lithium reagent (2) can be reacted in an inert solvent such as tetrahydrofuran (hereinafter referred to as "THF" ) , diethyl ether and dichloromethane, from under cooling to at room temperature, and if desired, under heat, to give an alcohol (3) . Then, (3) can be further reacted with an azidizing agent such as sodium azide and trimethylsilyl azide, in a solvent such as chloroform, 1, 2-dichloroethane, and toluene, in the presence of an acid such as trifluoroacetic acid, sulfuric acid, and methane sulfonic acid, from under cooling to at room temperature, and if desired, under heat, to give an azide (4). Further, (4) can be subjected to catalytic hydrogen reduction, under a hydrogen atmosphere from at normal pressure to under a pressurized condition, in an inert solvent such as ethanol, ethyl acetate, THF, and acetic acid, using a catalyst such as palladium-carbon, a Raney nickel, and platinum oxide, from at room temperature to under the heating condition, or subjected to hydride reduction in a solvent such as THF and diethyl ether, from under cooling to under heat, using a reducing agent such as lithium aluminum hydride, and (4) can be further reacted with a phosphine reagent such as triphenylphosphine, and tributyl phosphine, in a solvent such as THF, methanol, toluene, water, or a mixed solvent thereof, from at room temperature to under heat, to prepare a compound (lb) wherein in the compound (I) of the present invention, both of R10 and R11 are all hydrogen atoms.

Furthermore, (lb) can be reacted with aldehyde in the presence of palladium-carbon, a rhodium carbon catalyst, or the like, in a solvent such as ethanol and THF, under a hydrogen atmosphere, from at room temperature to under heat to prepare a compound (Ic) wherein in the compound (I) of the present invention, at least one of R10 and R11 is a lower alkyl group. In addition, the compound (I) of the present invention is represented by either the following general formula (lb) or (Ic) .

[0023] [Chem. 7] (lb) ( I c ) (Scheme 1) (wherein A, X, R1 to R3, and R6 to R9 each have the same meanings as described above. Further, R12 represents hydrogen or a lower alkyl group, R13 represents -CH2-R12 or a hydrogen atom, and M represents alkali metals such as lithium and magnesium halides)

[0024] The compounds (I) of the present invention may be subjected to reaction for group modification known to anyone skilled in the art to give a compound having a desired substituent. Typical reactions for it are described below.

Among the compounds (I) of the present invention, a compound wherein any one of R6 to R9 is a cyano group may be prepared by processing the corresponding compound where R6 to R9 are bromo groups with Zn(CN)2 in the presence of a catalyst such as Pd(PPh3)4 in a solvent such as DMF and N-methylpiperidone under heat.

Among the compounds (1) of the present invention, in case where X is C(R4) (R5) , a compound wherein any one of R3 to R6 is an aryl group which may be substituted, lower alkenyl group, or a lower alkynyl group can be prepared by reacting the corresponding compound where any one of R3 to R6 is a bromo group or an iodo group, with an arylboronic acid, an alkenylboronic acid, an alkynylboronic acid, or a boronate ester thereof in the presence of a catalyst such as Pd(PPh3)4, PdCl2(dppf), or Pd2 (dba) 3 along with a base such as K2C02, Na2C02, KOH, CsF, and NaOEt, in a solvent such as DMF, N-methylpiperidone, DME, and toluene, or a mixed solvent thereof with water, under heat (Suzuki reaction) .

[0025] Furthermore, the deprotection may be attained in a suitable solvent in the presence of a suitable base.

Specific examples of the base include NaOH, KOH, NaOMe, and NaOEt. Specific examples of the solvent include ethers such as THF, dioxane, and diglyme; alcohols such as MeOH, EtOH, and i-PrOH; MeCN, water; or a mixed solvent.

Depending on the type of the reaction substrate and the reaction condition, the solvent may be suitably selected. The reaction temperature may vary depending on the type of the starting compound and the reaction condition, generally covering from cooling to under reflux, preferably from about 0°C to about 100 °C.

In addition, the deprotection may also be attained in the presence of a metal catalyst such as Pd-C, Pd(OH)2, and PtC>2 in a suitable solvent under a hydrogen atmosphere, but may be attained in the presence of a suitable Lewis acid in a suitable solvent. Examples of the Lewis acid are BCI3, BBr3, and AICI3, and examples of the solvent are ethers such as THF, dioxane; esters such as ethyl acetate; alcohols such as MeOH, EtOH; MeCN; and a mixture thereof. Depending on the type of the reaction substrate and the reaction condition, the solvent may be suitably selected. The reaction temperature may vary depending on the type of the starting compound and the reaction condition, generally covering from cooling to under reflux, preferably from about -80°C to about 30°C.

Thus prepared, the compounds (I) of the present invention may be isolated as free compounds or as their pharmaceutically acceptable salts. A salt of the compounds (I) of the present invention may be prepared by processing the compounds (I) of the present invention that are in the form of free bases for ordinary reactions for salt formation .

[0026] The compound (I) of the present invention or a pharmaceutically acceptable salt thereof may be isolated and purified as their hydrates, solvates, or crystalline polymorphic substances. The isolation and purification may be attained through ordinary chemical treatment of extraction, concentration, evaporation, crystallization, filtration, recrystallization, and various types of chromatography .

Various isomers may be isolated by selecting suitable starting compounds, or by separating them based on the difference between the isomers in the physical or chemical properties thereof. For example, optical isomers may be led into stereochemical^ pure isomers by selecting suitable starting compounds or by racemic resolution of racemic compounds {for example, leading them into diastereomer salts with ordinary optically active acid for optical resolution) . 2, 2-Dimethyl-l-phenylindan-l-amine, 1- (4-fluorophenyl) -2 , 2-dimethylindan-l-amine, 1- (2-methoxy phenyl) -2, 2-dimethylindan-l-amine, l-(3-methoxy phenyl) -2, 2-dimethylindan-l-amine, 1, 2 , 2-trimethylindan-l-amine, 1 , 2, 2, 5-tetramethylindan-l-amine, 1, 2, 2, 6-tetramethylindan-1-amine, 4-fluoro-l, 2, 2-trimethylindan-l-amine, 5-fluoro-1,2, 2-trimethylindan-l-amine, 7-fluoro-l, 2, 2-trimethylindan-l-amine, 5-methoxy-l, 2, 2-trimethylindan-l-amine, 6-methoxy-l, 2, 2-trimethylindan-l-amine, 6-isopropoxy-1, 2, 2-trimethylindan-l-amine, l-ethyl-2,2-dimethylindan-l-amine, 1-iso propyl-2, 2-dimethylindan-l- 196136/2 amine, 11 -methyl-l ' , 3 ' -dihydrospiro [cyclopropan-1 , 2 ' -inden] -1 ' -amine, 2,4,5, 5-tetrarnethyl-5, 5-dihydro- H-cyclopenta [b] thiophen-4-amine of the compound of the present invention or a salt thereof can be subjected to optical resolution to its (R) -isomers and (S) -isomers by the above-described method.

[0027] The NMDA receptor antagonistic activity of the compounds of the present invention was confirmed by the following test methods. 1. MK-801 binding test: 1) Preparation of Specimens of Rat Meninges: The whole brain was taken out from 30 10-week SD rats (Nippon SLC) , and the cerebellum was removed from them. A 0.32 M sucrose solution was added to the part containing the cerebrum, cut in a mixer, and homogenized with a Teflon™ (trademark) homogenizer. This was centrifuged at 2800 rpm and 4°C for 15 minutes, and the resulting supernatant was again centrifuged at 25000 g and 4°C for 20 minutes. The pellets were suspended in 50 mM Tris-HCL (pH 7.5) containing 0.08% Triton X-100, and kept statically on ice for 30 minutes then centrifuged at 15000 g and 4°C for 20 minutes. The pellets were suspended in 50 mM Tris-HCl (pH-7.5) added thereto, and centrifuged at 15000 g and 4°C for 20 minutes. 50 mM Tris-HCl (pH 7.5) was again added to the pellets, and centrifuged in the same manner as before.

The pellets were suspended in 20 ml of 50 mM Tris-HCl (pH 7.5) added thereto, and homogenized with the Teflon™ (trademark) homogenizer . The membrane specimen was divided into small tubes and stored in a deep freezer (-80°C) .

Before use, this was washed twice with 5 mM Tris-HCl (pH 7.5) of five times that of the membrane specimen. Its concentration was controlled at 1 mg protein/ml with 5 mM Tris-HCl (pH 7.5) added to it, and this was used for assay.

[0028] 2) [3H] MK-801 binding Assay: 50 μΐ of the rat membrane specimen (1 mg protein/ ml) was added to a solution of a test compound dissolved in 1 μΐ of DMSO. Then, 50 μΐ of a ligand solution (600 nM glutamate, 600 nM glycine, 8 nM [3 H] MK-801 (Perkin-Elmer) was added to it and well stirred, and reacted at room temperature for 45 minutes. Using Uni Filter Plate GF/B 96 (Perkin-Elmer) previously coated with 0.2% polyethyleneimine, the membrane specimen was collected, and the filter was well washed with 5 mM Tris-HCl (pH 7.5). 30 μΐ of Microscinti 20 (Perkin-Elmer) was added to the filter, and the radioactivity trapped by the filter was determined by a microplate scintillation counter (TopCount™' by Beckman) . Based on the MK-801 (final 1 μΜ) inhibition, 100%, of a control case of DMSO alone, the concentration of the compound for 50% inhibition, IC50 was computed. The [3 H] MK-801 binding affinity for the rat membrane specimen was obtained to be Kd = 1.6 n through Scatchard analysis. The Ki value of the compound was computed according to the calculation equation: Ki = IC50/(1 + radioligand concentration (4 nM) in assay) /Kd value (1.6 nM) ) .

As a result, the compounds of the present invention exhibited good NMDA receptor affinity. The Ki values of the NMDA receptor affinity of some typical compounds of the present invention are shown in Table 1 below.

[Table 1]

[0029] 2. Intracellular Calcium Concentration Determination Test by FLIPR ( Fluorometric Imaging Plate Reader) : 1) Preparation of Rat First-Generation Neurocytes: Anesthetized with ether, Wistar rats (Nippon SLC) of pregnancy 19 days were let die from loss of blood by breast incision. The abdomen was cut open, and the womb was taken out, and the fetus was taken out of it. The whole brain was taken out, then the hemicerebrum was isolated in Neurobasal medium (Glu, Asp-free) (Gibco) , and the meninx was removed. The hemicerebrum was recovered by centrifugation, and suspended in a cell-dispersing solution (0.36 mg/ml papain, 150 U/ml DNase 1, 0.02% L-cysteine monohydrochloride monohydrate, 0.02% bovine serum albumin, 0.5% glucose, Ca2+, Mg2+-free PBS), and processed at 37°C for 15 minutes. This was centrifuged at 400 g for 5 minutes, and the supernatant was removed by suction. This was suspended in a neurocyte culture medium (Sumitomo Bakelite) , and the cell masses were removed by filtration. The number of the living cells was counted, and 100,000 cells/well were incubated on a 96-well plate (Biocoat PDL96W black/clear, by Nippon Becton Dickinson) (at 37 °C in 5% C02) .

[0030] 2) Intracellular Calcium Concentration Determination by FLIPR (Fluorometric Imaging Plate Reader) : The culture of rat first-generation neurocytes (DIV7- 9) was removed by suction, and the cells were washed once with a 100 μΐ assay buffer (Hank's Balanced Salt Solution (Ca2+, Mg 2+-free), 20 mM Hepes-NaOH (pH 7.4), 1 mM CaCl2) . 100 μΐ of the assay buffer containing Fluo3 (Dojin Chemical) was added thereto, and incubated for 1 hour (37°C, 5% CO 2) . The cells were washed three times with 100 196136 2 100 μΐ of the assay buffer, and then a compound solution dissolved in 1 μΐ of DMSO, and 100 μΐ of the assay buffer containing 2.5 μΜ (final concentration) tetrodotoxin were added to it and incubated for 30 minutes (37°C, 5% CO 2>■ The fluorescent intensity was measured at intervals of 2 seconds. Ten seconds after the measurement start, 50 μΐ of a ligand solution (Hank's Balanced Salt Solution (Ca 2+' Mg 2+-free) , 20 mM Hepes-NaOH (pH 7.4), 1 mM CaCl2, 9 μΜ NMDA, 30 μΜ glycine) containing the test compound solution dissolved in 0.5 μΐ of DMSO was added to it, and the fluorescent intensity of the system was measured for 120 seconds from the start of the measurement. The data measured for 120 seconds (60 times in total) were averaged. Based on the 10 μΜ M -801 inhibition with a control case of DMSO alone of 100%, the concentration of the compound for 50% inhibition, IC50, was computed.

As a result, the compounds of the present invention exhibited a good NMDA receptor antagonizing effect.

[0031] The pharmaceutical composition that contains, as an active component thereof, one or more of the compounds of the present invention and their pharmaceutically acceptable salts may be formulated, in conjunction with carriers and vehicles for ordinary pharmaceutical application and other additives, as tablets, powders, infinitesimal grains, granules, capsules, pills, liquids, injections, suppositories, ointments, and fomentations, and is administered orally or parenterally.

The clinical dose to human of the compound of the present invention may be suitably determined, depending on the symptom, the body weight, the age and the sex of a patient to whom the compound is applied. It may be usually from 0.1 to 500 mg/adult/day for oral administration, and from 0.01 to 100 mg/adult/day for non-oral administration, and this may be administered all at once or in several times. The dose may vary under various conditions, and as the case may be, it may be smaller than the above-mentioned dose range.

The solid composition for oral administration of the compound of the present invention may be tablets, powders, granules, or the like. In the solid composition, one or more active substances may be mixed with at least one inert diluent, such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, and magnesium metasilicate aluminate. According to an ordinary manner, the composition may contain any other additive than such an inert diluent, for example, a lubricant such as magnesium stearate, a disintegrator such as calcium cellulose glycolate, a stabilizer such as lactose, a solubilizer, and a solubilizing adjuvant such as glutamic acid and aspartic acid. The tablets and pills may be coated with a sugar or with a gastric-coating or enteric-coating film.

[0032] The liquid composition for oral administration includes pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs, and contains ordinary inert diluents such as purified water and ethyl alcohol. The composition may contain any other additives than such an inert diluent, for example, auxiliary agents such as a solubilizer, a dissolution promoter, a wetting agent, a suspending agent, as well as a sweetener, a flavoring, a fragrance, and a preservative. The injection for non-oral administration includes sterilized aqueous or non-aqueous solutions, suspensions, and emulsions. The diluent for the aqueous solution and suspension include, for example, distilled water for injection and physiological saline. The diluent for the non-aqueous solution and suspension includes, for example, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, alcohols such as ethyl alcohols, Polysorbate 80 (trade name) .

The composition may further contain any other additive such as an isotonizer, a preservative, a wetting agent, an emulsifier, a dispersant, a stabilizer, a solubilizer, and a dissolution promoter. These may be sterilized by filtration through a bacteria-trapping filter, or by addition of a germicide, or through irradiation with light. As the case may be, a germ-free solid composition may be prepared, and it may be dissolved in germ-free water or germ-free solvent for injection to give the intended liquid composition before use. '5 EXAMPLES

[0033] Hereinbelow, the compounds of the present invention are described with reference to the following Examples. 0 The starting compounds for the compounds of the present invention include novel compounds, and thus their production examples are illustrated as Reference Examples. Reference Example 1 To a solution of 3-hydroxymethylindan-l-one (1.23 g) 5 and methyl iodide (4.31 g) in THF (20 ml) was added 55% oily sodium hydride (1.33 g) under ice-cooling, followed by stirring at the same temperature for 1 hour. To the reaction liquid was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl 0 acetate, washed with saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=10 : 1) to obtain a compound of Reference Example 1 . 5 as an oily substance.

Reference Example 2 To a solution of t-BuO (3.0 g) in THF (7 ml) was added a solution of methyl 3-oxoindane-l-carboxylate (1.0 g) in THF {2 ml) at -20 °C, followed by stirring at the same temperature for 30 minutes. To this was added methyl iodide (4.5 g) , followed by stirring for 30 minutes while warming to room temperature. The reaction liquid was ice-cooled, and partitioned between 1 N hydrochloric acid and ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a compound of Reference Example 2 (1.2 g) as an oily substance .

Reference Example 3 To a solution of the compound of Reference Example 2 (3.2 g) in D SO (20 ml) was added LiCl (1.2 g) , followed by stirring at 200°C for 2 hours. After cooling the reaction, it was partitioned between 1 N hydrochloric acid and ethyl acetate, and the organic layer was washed with water and saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=4:l) to obtain a compound of Reference Example 3 (1.9 g) as an oily substance. 196136 2

[0034] Reference Example 4 To a solution of the compound of Reference Example 2 (2.6 g) in methanol (30 ml) was added sodium borohydride (2.1 g) under ice-cooling, followed by heating under reflux for 30 minutes. The reaction liquid was cooled, followed by addition of a saturated aqueous ammonium chloride solution and extraction with ethyl acetate. Further, it was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a compound of Reference Example 4 (2.0 g) as an oily substance.

Reference Example 5 A compound of Reference Example 5 was prepared from the compound of Reference Example 4 in the same manner as in Reference Example 1.

Reference Example 6 To a solution of the compound of Reference Example 5 (0.99 g) in methanol (8 ml) was added a 10 M aqueous sodium hydroxide solution (8 ml) , followed by stirring at 60°C for 12 hours. Methanol was evaporated under reduced pressure, and then ice-cooled, followed by addition of concentrated hydrochloric acid for neutralization and further stirring at room temperature for 1 hour. The precipitate was collected by filtration, and dried under reduced pressure to obtain a compound of Reference Example 6 (0.94 g) as a colorless amorphous substance.

Reference Example 7 To a solution of the compound of Reference Example 6 (0.94 g) and ammonium chloride (0.64 g) , 1-hydroxybenzotriazole (0.54 g) in DMF (10 ml) was added N- [3- (dimethylamino) propyl] -N ' -ethylcarbodiimide hydrochloride (1.2 g) , followed by stirring at room temperature for 3 days. To this was added saturated aqueous ammonia solution, followed by stirring for one more day, and then the precipitate was collected by filtration, and dried under reduced pressure to obtain a compound of Reference Example 7 (0.62 g) as a colorless crystal, Reference Example 8 The present compound was prepared from 4-methylindan- 1-one in the same manner as in Reference Example 2.

Reference Example 9 The present compound was prepared from 4-trifluoromethylindan-l-one in the same manner as in Reference Example 2.

[0035] Reference Example 10 The present compound was prepared from 5-trifluoromethylindan-l-one in the same manner as in Reference Example 2.

Reference Example 11 To 3- (3-trifluoromethylphenyl) propionic acid was added trifluoromethanesulfonic acid at room temperature, followed by stirring at 60 °C for 3 hours. The reaction liquid was put into cold water, followed by extraction with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=9:l to 5:1) to obtain 5-trifluoromethylindahe (2.2· g) and a compound of Reference Example 11 (0.70 g) as colorless solids, respectively.

Reference Example 12 The present compound was prepared from the compound of Reference Example 11 in the same manner as in Reference Example 2.

Reference Example 13 To a solution of 7-bromo-4-fluoro-2, 2-dimethylindan-1-one (3.7 g) in toluene (30 ml) were added tributyl (vinyl) tin (7.0 g) , tris (dibenzylideneacetone) dipalladium (0.40 g) , and a 0.49 solution (2.7 ml) of tri (t-butyl) phosphine in n-hexane, at followed by stirring at 70°C for 12 hours. The reaction liquid was cooled, and a saturated aqueous potassium fluoride solution was added thereto, followed by stirring at room temperature for 30 minutes. Then, the insoluble materials were removed by filtration through Celite. The filtrate was extracted with ethyl acetate, washed with saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=10 : 1) to obtain a compound of Reference Example 13 (1-7 g) as an oily substance.

Reference Example 14 A solution of 2-bromo-5-fluorobenzaldehyde (1.5 g), malonic acid (1.5 g) , and piperidine (0.07 ml) in pyridine (10 ml) was heated for 1 day under reflux. The reaction liquid was concentrated under reduced pressure, 1 N hydrochloric acid was then added thereto for neutralization, and crystallized precipitates were collected by filtration. This was dissolved in methanol (10 ml), and a 5% rhodium carbon catalyst (150 mg) was added thereto, followed by stirring at room temperature for 12 hours under a hydrogen atmosphere (1 atm) . The insoluble materials was removed by filtration through Celite, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10 : 1 ) to obtain a compound of Reference Example 14 (0.50 g) as a colorless solid.

[0036] Reference Example 15 The present compound was prepared from the compound of Reference Example 14 in the same manner as in Reference Example 11.

Reference Example 16 The present compound was prepared from the compound of Reference Example 15 in the same manner as in Reference Example 1.

Reference Example 17 The present compound was prepared from 3- {3-bromo-5-methoxy phenyl) propionic acid in the same manner as in Reference Example 11.

Reference Example 18 The present compound was prepared from the compound of Reference Example 17 in the same manner as in Reference Example 2.

Reference Examples 19 to 25 The present compound was prepared from each of the corresponding indanone and a Grignard reagent in the same manner as in Reference Example 28.

Reference Example 26 The present compound was prepared from l-bromo-2-fluorobenzene and the corresponding indanone in the same manner as in Reference Example 29.

Reference Example 27 The present compound was prepared from each of the corresponding indanone and a Grignard reagent in the same manner as in Reference Example 28.

Reference Example 28 To a solution of 2 , 2-dimethylindan-l-one (0.63 g) in THF was added a 1 M solution of (4-fluorophenyl) magnesium bromide in THF (7.8 ml) at room temperature, followed by stirring at the same temperature for 2 hours. To the reaction liquid was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=30: 1) to obtain a compound of Reference Example 28 (0.99 g) as an oily substance.

Reference Example 29 To a solution of 2-bromoanisole (1.4 g) in diethyl ether (10 ml) was added a 1.6 M solution (4.6 ml) of n-butyl lithium in n-hexane at -78 °C, followed by stirring at the same temperature for 1 hour. To this was added 2,2-dimethylindan-l-one (0.60 g) , followed by further stirring at the same temperature for 1 hour. A saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=30 : 1) to obtain a compound of Reference Example 29 (0.62 g) as an oily substance.

[0037] Reference Example 30 The present compound was prepared from each of the corresponding indanone and a Grignard reagent in the same manner as in Reference Example 28.

Reference Examples 31 and 32 The present compound was prepared from each corresponding indanone in the same manner as in Reference Example 29.

Reference Examples 33 to 41 The present compound was prepared from each corresponding indanone in the same manner as in Reference Example 42.

Reference Example 42 To a solution of 2, 2, 6-trimethylindan-l-one (1.8 g) in THF (35 ml) was added a 1.4 M solution (15 ml) of methyl magnesium bromide in THF/toluene (25:75), and warmed to room temperature, followed by stirring for 2 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added thereto under ice-cooling, followed by stirring, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=10: 1) to obtain a compound of Reference Example 42 (1.9 g) as an oily substance.

Reference Example 43 To a solution of 6-methoxy-2, 2-dimethylindan-l-one (2.2 g) in THF (40 ml) was added a 1.4 M solution (17 ml) of methyl magnesium bromide in THF/toluene (25:75) under ice-cooling, and warmed to room temperature, followed by stirring for 2 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added thereto under ice-cooling, followed by stirring and extraction with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=10: 1) to obtain a compound of Reference Example 43 (2.3 g) as an oily substance.

Reference Example 44 To a solution of 6-fluoro-2, 2-dimethylindan-l-one (0.47 g) in THF (9 ml) was added a 0.96 M solution (5.5 ml) of methyl magnesium bromide in THF under ice-cooling, followed by warming to room temperature and stirring for 2 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added thereto under ice-cooling, followed by stirring and extraction with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=10 : 1 ) to obtain a compound of Reference Example 44 (0.45 g) as an oily substance.

[0038] Reference Example 45 To a solution of 6-bromo-2, 2-dimethylindan-l-one (3.8 g) in THF (60 ml) was added a 1.4 M solution (17 ml) of methyl magnesium bromide in THF/toluene (25:75) under ice-cooling, followed by warming to room temperature and stirring for 2 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added thereto under ice-cooling, followed by stirring arid extraction with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=5:l) to obtain a compound of Reference Example 45 (3.8 g) as an oily substance.

Reference Example 46 To a solution of 2, 2-dimethyl-6-trifluoromethylindan-1-one (1.7 g) in THF (15 ml) was added a 1.4 M solution (10 ml) of methyl magnesium bromide in THF/toluene (25:75) under ice-cooling, followed by warming to room temperature and stirring for 1 hour. After completion of the reaction, a saturated aqueous ammonium chloride solution was added thereto under ice-cooling, followed by stirring and extraction with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=6:l) to obtain a compound of Reference Example 46 (1.7 g) as an oily substance.

Reference Examples 47 to 54 The present compound was prepared from the corresponding indanone in the same manner as in Reference Example 42.

[0039] Reference Example 55 To a solution of 2, 2-dimethylindan-l-one (2.0 g) and trimethyl (trifluoromethyl) silane (2.7 g) in THF (20 ml) was added a 1 M solution (12 ml) of tributyl ammonium fluoride in THF under ice-cooling, followed by slowly warming to room temperature and stirring for 5 hours. 1 N hydrochloric acid was added thereto, followed by extraction with diethyl ether, washing with a saturated aqueous sodium chloride solution, and then drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=10: 1) to obtain a compound of Reference Example 55 (2.9 g) as an oily substance.

Reference Example 56 To a solution of 2, 2-dimethylindan-l-one (2.0 g) in THF (20 ml) was added a 0.5 M solution of ethyllithium in benzene/cyclohexane (9:1) (37 ml) at -78°C, followed by stirring at the same temperature for 2 hours. To the reaction liquid was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate, and drying over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=3:l) to obtain a compound of Reference Example 56 (2.1 g) as an oily substance.

Reference Example 57 The present compound was prepared from the corresponding indanone in the same manner as in Reference Example 56.

Reference Example 58 to 61 The present compound was prepared from the corresponding indanone and Grignard reagent in the same manner as in Reference Example 42.

[0040] Example 1 2, 2-Dimethyl-l-phenylindan-l-amine monofumarate To a solution of 2, 2-dimethyl-l-phenylindan-l-ol (736 mg) in chloroform (10 ml) were added sodium azide (412 mg) and trifluoroacetic acid (1.4 ml) under ice-cooling, followed by stirring at the same temperature for 2 hours. It was alkalified by addition of 10% aqueous ammonia, and then extracted with ethyl acetate, and the organic layer was washed with saturated brine. The solvent was evaporated under reduced pressure to obtain an azide (798 mg) . Thereafter, this was dissolved in methanol (10 ml) , and 10% palladium/carbon (85 mg) was added thereto, followed by stirring at room temperature for 3 days under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane: ethyl acetate=30:l to 5:1) to obtain an amine (437 mg) . A portion thereof (119 mg) and fumaric acid (59 mg) were dissolved in methanol, and the solvent was then evaporated under reduced pressure. The residue was recrystallized from acetone to obtain a compound of Example 1 (168 mg) as a colorless crystal.

Example 2 The present compound was prepared in the same manner as in Example 1.

Example 3 cis-3- (Methoxymethyl) -2 , 2-dimethyl-l-phenylindan-l-amine hydrochloride Example 4 trans-3-Hydroxy methyl-2 , 2-dimethyl-l-phenylindan-l-amine hydrochloride To a solution of the compound of Reference Example 20 (1.8 g) in methylene chloride (30 ml) were added sodium azide (1.3 g) and trifluoroacetic acid (2.5 ml), followed by stirring at the same temperature for 30 minutes. It was alkalified by addition of 10% aqueous ammonia, and extracted with ethyl acetate, and the organic layer was washed with saturated brine. The solvent was evaporated under reduced pressure to obtain an azide. Thereafter, this was dissolved in methanol (30 ml) , and 10% palladium/carbon (0.5 g) was added thereto, followed by stirring at room temperature for 4 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent chloroform:methanol=20 : 1) to obtain an amine (1.2 g) .

Further, a portion thereof (1.1 g) was dissolved in methylene chloride (10 ml), and a 1 M solution (4.5 ml) of boron tribromide in methylene chloride was added thereto under ice-cooling, followed by stirring for 2 hours. To the reaction liquid were added alumina and methanol, followed by stirring at room temperature for 1 hour, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol= : 1) to obtain free forms of the compounds of Examples 3 and 4, respectively. To each of the solutions in ethyl acetate was added a 4 N solutions of HC1 in ethyl acetate, and the solvent was then evaporated under reduced pressure. The residue was crystallized from n-hexane to obtain a compound of Example 3 (350 mg), and a compound of Example 4 (97 mg) as colorless crystals, respectively.

[0041] Example 5 trans-2-Methyl-l, 2-diphenylindan-l-amine hydrochloride Example 6 cis-2-Methyl-l, 2-diphenylindan-l-amine hydrochloride A hydrochloride of a diastereomer mixture obtained in the same manner as in Example 17 from 1, 2-diphenylindan-l-ol was recrystallized from ethanol to obtain a compound of Example 5, and further, the filtrate was concentrated under reduced pressure, and then was purified by alumina/silica gel column chromatography (eluent; chloroform) . Thus obtained residue was crystallized from n-hexane to make its hydrochloride by an ordinary method, thereby obtaining a compound of Example 6 as a colorless crystal, respectively. Examples 7 and 8 The present compounds were prepared in the same manner as in Example 1.

Example 9 The present compound was prepared in the same manner as in Example 21.

Example 10 N, 2, 2-trimethyl-l-phenylindan-l-amine hydrochloride To a solution of a desalted compound of Example 1 (125 mg) in ethanol (5 ml) were added an aqueous 37% formaldehyde solution (0.2 ml) and 10% palladium/carbon, followed by stirring at room temperature for 1 day under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure, and then partitioned between a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=20:l to 5:1). Then, the residue was dissolved in a 4 N solution of HC1 in ethyl acetate, and the solvent was evaporated under reduced pressure. The residue was washed with a mixed solvent of diisopropyl ether and 1,4-dioxane to obtain a compound of Example 10 (115 mg) as a colorless crystal .

Example 11 The present compound was prepared by reacting for a longer time in the same manner as in Example 10.

Examples 12 to 16 The present compounds were prepared in the same manner as in Example 17.

[0042] Example 17 1- (4-Fluorophenyl) ~2 , 2-dimethylindan-l-amine monofumarate To a solution of the compound of Reference Example 28 (984 mg) in chloroform (12 ml) were added sodium azide (500 mg) and trifluoroacetic acid (1.7 ml) under ice-cooling, followed by stirring at room temperature for 3 hours. It was alkalified by addition of 10% aqueous ammonia, and extracted with chloroform, and then the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=40: 1) to obtain an azide {1.08 g) . Thereafter, this was dissolved in methanol (13 ml) , and 10% palladium/carbon (102 mg) was added thereto, followed by stirring at room temperature for 3 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=30:l to 5:1) to obtain an amine (562 mg) . A portion thereof (100 mg) and fumaric acid (51 mg) were dissolved in methanol, and the solvent was then evaporated under reduced pressure. The residue was washed with a mixed solvent of diisopropyl ether and 1,4-dioxane to obtain a compound of Example 17 (127 mg) as a colorless crystal.

[0043] Example 18 1- (2- ethoxy phenyl ) -2, 2-dimethylindan-l-amine hydrochloride To a solution of the compound of Reference Example 29 (620 mg) in chloroform (9 ml) were added sodium azide (304 mg) and trifluoroacetic acid (1 ml) under ice-cooling, followed by stirring at room temperature for 3 hours. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane: ethyl acetate=30: 1) to obtain an azide (635 mg) . Thereafter, this was dissolved in methanol (8 ml), and 10% palladium/carbon (62 mg) was added thereto, followed by stirring at room temperature for 3 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol=30 : 1) to obtain an amine (357 mg) . Further, this was dissolved in ethyl acetate, a 4 N solution of HC1 in ethyl acetate was added thereto, and the solvent was evaporated under reduced pressure. The residue was washed with n-hexane to obtain a compound of Example 18 (231 mg) as a colorless crystal.

Examples 19 and 20 The present compounds were prepared in the same manner as in Example 18.

[0044] Example 21 1- (3-Hydroxyphenyl) -2, 2-dimethylindan-l-amine To a solution of the compound of Example 19 (150 mg) in methylene chloride (2 ml) was added a 1 M solution of boron tribromide in methylene chloride (0.67 ml) under ice- cooling, followed by stirring for 2 hours. A saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with chloroform, and drying over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=l:l to 0:1) to obtain a compound of Example 21 (51 mg) as a colorless amorphous substance.

Example 22 The present compound was prepared in the same manner as in Example 18.

Example 23 1,2, 2-Trimethylindan-l-amine hydrochloride To a solution of 1, 2, 2-trimethylindan-l-ol (406 mg) in chloroform (6 ml) were added sodium azide (300 mg) and trifluoroacetic acid (1 ml) under ice-cooling, followed by stirring at room temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (6 ml), and 10% palladium-carbon (40 mg) was added thereto, followed by stirring at room temperature for 3 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane: ethyl acetate=30:l to 5:1) to obtain an amine (140 mg) as an oily substance. Further, this was dissolved in ethyl acetate, a 4 N solution of HC1 in ethyl acetate was added thereto, and the solvent was evaporated under reduced pressure. The residue was crystallized from diisopropyl ether to obtain a compound of Example 23 (153 mg) as a colorless crystal.

Example 24 cis-1, 2, 2, 3-Tetramethylindan-l-amine hydrochloride Example 25 trans-1, 2,2, 3-Tetramethylindan-l-amine hydrochloride The same procedure as in Example 23 using the compound of Reference Example 33 was carried out, and the resulting diastereomer was separated, and purified by silica gel column chromatography (eluent; chloroform:methanol : saturated aqueous ammonia=50 : 1 : 0.1 to :1:0.1), and each was made into its hydrochloride by an ordinary method, thereby obtaining a compound of Example 24, and a compound of Example 25 as colorless crystals, respectively.

Example 26 The present compound was prepared in the same manner as in Example 23.

[0045] Example 27 cis-3-Methoxy-l, 2, 2-trimethylindan-l-amine hydrochloride To a 3 N aqueous solution (10 ml) of sodium hydroxide were added bromine (0.18 ml) and the compound of Reference Example 7 (0.62 g) under ice-cooling, followed by stirring at room temperature for 3 days. An aqueous a2S03 solution was added thereto, followed by stirring, extraction with methylene chloride, and washing with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=4 : 1) , and thereafter, by neutral silica gel column chromatography (eluent; chloroform:methanol : saturated brine=50 : 1 : 0.1) to obtain an amine (179 ml) as an oily substance. This was made into its hydrochloride, and then crystallized from n-hexane to obtain a compound of Example 27 (89 mg) as a colorless crystal.

[0046] Example 28 1,2,2, 4-Tetramethylindan-l-amine hydrochloride Example 29 4-Fluoro-l, 2, 2-trimethylindan-l-amine hydrochloride Example 30 4-Trifluoromethyl-1, 2, 2-trimethylindan-l-amine hydrochloride Example 31 1, 2, 2 , 5-Tetramethylindan-l-amine hydrochloride Example 32 -Methoxy-l, 2, 2-trimethylindan-l-amine hydrochloride Example 33 -Fluoro-l, 2 , 2-trimethylindan-l-amine · hydrochloride Example 34V -Chloro-l, 2, 2-trimethylindan-l-amine hydrochloride Example 35 -Trifluoromethyl-1, 2, 2-trimethylindan-l-amine hydrochloride The compounds of Examples 28 to 35 as described above were prepared from the corresponding alcohols in the same manner as in Example 23.

Example 36 1, 2,2, 6-Tetramethylindan-l-amine · hydrochloride To a solution of the compound of Reference Example 42 (1.9 g) in chloroform (38 ml) were added sodium azide (1.3 g) and trifluoroacetic acid (4.6 mg) under ice-cooling, followed by stirring at the same temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (38 ml), and 10% palladium-carbon (200 mg) was added thereto, followed by stirring at room temperature for 12 hours under a hydrogen atmosphere (normal pressure) , The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform: methanol=10: 1) to obtain an amine (720 mg) as an oily substance. Further, this was dissolved in ethyl acetate, a 4 N HCl solution in ethyl acetate was added thereto, and the solvent was evaporated under reduced pressure. The residue was crystallized from n-hexane/diethylether to obtain a compound of Example 36 (227 mg) as a colorless crystal.

[0047] Example 37 6-Hydroxy-l , 2 , 2-trimethylindan-l-amine hydrochloride To a solution of a free form (96 mg) of the compound of Example 38 in 1, 2-dichloroethane (2 ml) was added a 1 M boron tribromide solution in methylene chloride (0.5 ml) under ice-cooling, followed by stirring at room temperature for 3 hours. To the reaction liquid was slowly added water under ice-cooling and stirred, followed by extraction with ethyl acetate, and then washing with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was recrystallized from diisopropyl ether to obtain an amine (48 mg) as a colorless crystal. Further, this was made into its hydrochloride by an ordinary method, and then crystallized from a mixed solvent of diethylether and n-hexane to obtain a compound of Example 37 (47 mg) as a colorless crystal.

Example 38 6-Methoxy-l , 2 , 2-trimethylindan-l-amine hydrochloride To a solution of the compound of Reference Example 43 (2.3 g) in chloroform (40 ml) were added sodium azide (1.4 g) and trifluoroacetic acid (4.8 ml) under ice-cooling, followed by stirring at the same temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (25 ml), and 10% palladium-carbon (330 mg) was added thereto, followed by stirring at room temperature for 12 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform: methanol=10 : 1) to obtain an amine (1.1 g) as an oily substance. Further, a portion thereof (270 mg) was made into its hydrochloride by an ordinary method, and recrystallized from a mixed solvent of diethylether and ethyl acetate to obtain a compound of Example 38 (107 mg) as a colorless crystal. Example 39 The present compound was prepared in the same manner as in Example 40.

[0048] Example 40 6-Isopropoxy-l , 2, 2-trimethylindan-l-amine hydrochloride To a solution of a free form (179 mg) of the compound of Example 37 in THF (3 ml) were added 2-propanol (5 ml), diethylazodicarboxylate (0.55 ml), and triphenylphosphine (300 mg) , followed by stirring at room temperature for 1 day. The reaction liquid was concentrated under reduced pressure, and then partitioned between ethyl acetate and 1 N hydrochloric acid. The aqueous layer was neutralized with a 1 N aqueous sodium hydroxide solution, followed by extraction with ethyl acetate, washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=10 : 1) to obtain an isopropoxy derivative (171 mg) as an oily substance. This was made into its hydrochloride by an ordinary method, and then crystallized from diethylether to obtain a compound of Example 40 (128 mg) as a colorless crystal.

Example 41 6-Fluoro-l, 2, 2-trimethylindan-l-amine hydrochloride To a solution of a compound of Reference Example 44 (444 mg) in chloroform (8 ml) were added sodium azide (300 mg) and trifluoroacetic acid (1 ml) under ice-cooling, followed by stirring at room temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (6 ml), and 10% palladium-carbon (80 mg) was added thereto, followed by stirring at room temperature for 3 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=l:l) to obtain an amine (327 mg) as an oily substance. Further, this was dissolved in ethyl acetate, a 4 N HC1 solution in ethyl acetate was added thereto, and the solvent was evaporated under reduced pressure. The residue was crystallized from diethylether to. obtain a compound of Example 41 (310 mg) as a colorless crystal.

Example 42 6-Bromo-l, 2,2, -trimethylindan-l-amine hydrochloride To a solution of a compound of Example 45 (3.8 g) in chloroform (60 ml) were added sodium azide (1.9 g) and trifluoroacetic acid (3.4 ml) under ice-cooling, followed by stirring at the same temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (50 ml), and triphenylphosphine (7.8 g) was added thereto, followed by heating under reflux for 1 day.

Since the reaction was not completed, tributylphosphine (3.0 g) was further added thereto, followed by stirring at room temperature for 3 hours, and then the reaction liquid was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform: methanol=10 : 1) to obtain an amine (1.2 g) as an oily substance. Further, a portion thereof (204 mg) was made into its hydrochloride by an ordinary method, and recrystallized from ethyl acetate to obtain a compound of Example 42 (222 mg) as a colorless crystal.

[0049] Example 43 6-Trifluoromethyl-1, 2, 2-trimethylindan-l-amine hydrochloride To a solution of a compound of Example 46 (1.6 mg) in methylene chloride (20 ml) were added sodium azide (0.85 g) and trifluoroacetic acid (2.5 ml) under ice-cooling, followed by stirring at the same temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (100 ml), and 10% palladium-carbon (0.5 g) was added thereto, followed by stirring at room temperature for 15 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was partitioned between 1 N hydrochloric acid and ethyl acetate, and the aqueous layer was alkalified with sodium hydrogen carbonate, extracted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain an amine (1.1 g) as an oily substance. Further, this was made into its hydrochloride by an ordinary method, and then crystallized from a mixed solvent of n-hexane and diethylether to obtain a compound of Example 43 (1.1 g) as a colorless crystal.

Example 44 6-Cyano-l, 2, 2-trimethylindan-l-amine hydrochloride To a solution of a free form of the compound of Example 42 (112 mg) in N-methylpyrrolidone were added zinc cyanide (63 mg) , calcium hydroxide (40 mg) and tetrakis (triphenylphosphine) palladium (150 mg) , followed by stirring under heat at 110 °C for 1 day. The reaction liquid was cooled, and then ethyl acetate and water were added thereto, followed by stirring. The insoluble materials were removed by filtration through Celite. The filtrate was separated out, and the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel chromatography (eluent; chloroform:methanol=10 : 1) to obtain a cyano derivative form (78 mg) as an oily substance.

Further, this was made into its hydrochloride by an ordinary method, and crystallized from ethyl acetate to obtain a compound of Example 44 (79 mg) as a colorless crystal .

[0050] Example 45 1,2, 2-Trimethyl-6-vinylindan-l-amine hydrochloride 196136/2 To a solution of a free form of the compound of Example 42 {0.67 g) in toluene (7 ml) were added tributyl (vinyl) tin {1.3 g) , tris (dibenzylideneacetone) dipalladium (0.15 g) and tri(t-butyl) phosphine (0.32 g), followed by stirring under heat at 70°C for 2 hours. An aqueous potassium fluoride solution was added thereto, followed by stirring for 1 hour, and the insoluble materials were removed by filtration through Celite. The filtrate was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=8:l) to obtain an amine (349 mg) as an oily substance. Further, a portion thereof (157 mg) was made into its hydrochloride by an ordinary method, and crystallized from n-hexane to obtain a compound of Example 45 (38 mg) as a colorless crystal.

Example 46 1 , 2, 2-Trimethyl-6- (piperidin-l-yl ) indan-l-amine hydrochloride.

To a solution of a free form of the compound of Example 42 (144 mg) in toluene (3 ml) were added piperidine (0.07 ml), palladium diacetate (7 mg) , sodium t-butoxide (81 mg) , and tri (2-methylphenyl) phosphine (18 mg) , followed by stirring under heat at 80°C for 1 day. The reaction liquid was cooled, and then partitioned between ethyl acetate and water, and the organic layer was washed saturated brine. It was dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; chloroform:methanol=10 : 1) to obtain an amine {75 mg) as an oily substance. Further, this was made into its dihydrochloride by an ordinary method, and crystallized from ethyl acetate to obtain a compound of Example 46 (61 mg) as a colorless crystal.

Example 47 The present compound was prepared from compound of Example 47 in the same manner as in Example 41.

Example 48 7-Fluoro-l, 2, 2-trimethylindan-l-amine hydrochloride To a solution of the compound of Reference Example 51 (774 mg) in chloroform (15 ml) were added sodium azide (370 mg) and trifluoroacetic acid (1.3 ml) under ice-cooling, followed by stirring at the same temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide (700 g) . Then, a portion thereof (480 mg) was dissolved in methanol (10 ml), and 10% palladium-carbon (50 mg) was added thereto, followed by stirring at room temperature for 1 day under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure to obtain an oily substance. This was made into its hydrochloride by an ordinary method, and crystallized from ethyl acetate to obtain a compound of Example 48 (55 mg) as a colorless crystal .

[0051] Example 49 The present compound was prepared in the same manner as in Example 41.

Example 50 The present compound was prepared in the same manner as in Example 42.

Example 51 7-Ethyl-4-fluoro-1, 2, 2-trimethylindan-l-amine hydrochloride To a solution of a free form of the compound of Example 52 (79 mg) in methanol (20 ml) was added 10% palladium-carbon (50 mg), followed by stirring at room temperature for 12 hours under a hydrogen atmosphere (normal pressure) . The insoluble materials were removed by filtration through Celite, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 1 chloroform: methanol=10 : 1 ) and then made into its hydrochloride by an ordinary method to obtain a compound of Example 51 (53 mg) as a pale yellow amorphous substance. Examples 52 and 53 The present compounds were prepared in the same manner as in Example 43.

Example 54 The present compound was prepared in the same manner as in Example 41.

Example 55 The present compound was prepared in the same manner as in Example 42.

Example 56 The present compound was prepared in the same manner as in Example 41.

Example 57 2 , 2-Dimethyl-l-trifluoromethylindan-l-amine hydrochloride To a solution of the compound of Example 55 (2.3 g) in chloroform (30 ml) were added sodium azide (1.3 g) and concentrated sulfuric acid (1.6 ml) under ice-cooling, followed by stirring at room temperature for 2 hours. The reaction solution was further ice-cooled, and 10% aqueous ammonia was added thereto, followed by stirring and extraction with chloroform. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (20 ml), and 10% palladium-carbon (200 mg) was added thereto, followed by stirring at room temperature for 12 hours under a hydrogen atmosphere (normal pressure) . The insoluble materials were removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, followed by extraction with 1 M hydrochloric acid. The aqueous layer was alkalified with 1 M sodium hydroxide, and extracted with ethyl acetate. It was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain an amine (1.17 g) . This was made into its hydrochloride by an ordinary method, and then crystallized from a mixed solvent of diethylether and ethyl acetate to obtain a compound of Example 57 (234 mg) as a colorless crystal.

[0052] Example 58 l-Ethyl-2, 2-dimethylindan-l-amine hydrochloride To a solution of a compound of Reference Example 56 (606 mg) in chloroform (9 ml) were added sodium azide (414 mg) and trifluoroacetic acid (1.4 ml) under ice-cooling, followed by stirring at room temperature for 1 hour. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure to obtain an azide. Then, this was dissolved in methanol (9 ml), and 10% palladium-carbon (700 mg) was added thereto, followed by stirring at room temperature for 3 hours under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=5:l) to obtain an amine (339 mg) as an oily substance. Further, this was made into its hydrochloride by an ordinary method, and then crystallized from diisopropyl ether to obtain a compound of Example 58 (190 mg) as a colorless crystal.

Example 59 The present compound was prepared in the same manner as in Example 58.

Example 60 l-Isopropyl-2 , 2-dimethylindan-l-amine hydrochloride To a solution of l-isopropyl-2, 2-dimethylindan-l-ol (175 mg) in chloroform (3 ml) were added sodium azide (114 mg) and trifluoroacetic acid (0.4 ml) under ice-cooling, followed by stirring at room temperature for 3 days. It was alkalified by addition of 10% aqueous ammonia, and then extracted with chloroform, and the organic layer was washed with saturated brine. It was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=30 : 1 ) to obtain an azide (106 mg) as an oily substance. Then, this was dissolved in methanol (3 ml), and 10% palladium-carbon (15 mg) was added thereto, followed by stirring at room temperature for 1 day under a hydrogen atmosphere (normal pressure) . The reaction mixture was filtered through Celite, and the solvent was evaporated under reduced pressure to obtain an amine (71 mg) as an oily substance. Further, a portion thereof (20 mg) was made into its hydrochloride by an ordinary method, and crystallized from diisopropyl ether to obtain a compound of Example 60 (16 mg) as a colorless crystal.

Examples 61 to 63 The present compound was prepared in the same manner as in Example 60.

[0053] Example 64 trans-2-Ethyl-l, 2-dimethylindan-l-amine hydrochloride Example 65 cis-2-Ethyl-l, 2-dimethylindan-l-amine hydrochloride The same procedure as in Example using the compound of Reference Example 60 was carried out, and the resulting diastereomer was separated and purified by basic silica gel column chromatography (eluent; n-hexane : ethyl acetate=20:l 196136/2 to 10:1), and the resulting amine was made into its hydrochloride by an ordinary method, thereby obtaining a compound of Example 64 and a compound of Example 65, as colorless amorphous substances, respectively.

Example 66 1 ' -Methyl-1 ' , 3 ' -dihydrospiro [cyclopropan-1 , 2 '-inden] -1 ' -amine hydrochloride.

Example 67 1 ' -Methyl-1 ' , 3 ' -dihydrospiro [cyclopentan-1, 2 ' -inden] -1 ' -amine hydrochloride.

The present compound was prepared in the same manner as in Example 58.

Examples 68 and 69 The present compounds were prepared in the same manner as in Example 58.

[0054] The structural formulae and the physicochemical data of the compounds of the above Reference Examples and the compounds of the above Examples are shown in the following Tables 2 to 14. The compounds shown in Table 15 may be readily produced similarly to the above Examples or Production Processes or according to the modifications apparent to one skilled in the art. The symbols in the Tables have the following meanings.

Rf.: Reference Example, Ex.: Example, STRUCTURE: structural formula, DATA: data, SALT: salt, Ph: phenyl, Me: methyl, Et: ethyl, OMe: methoxy, thienyl: thienyl, iPr: isopropyl, vinyl: vinyl, 1-Pip: 1-piperidinyl, n-Bu: norma butyl, c-Hex: cyclohexyl, c-Pr: cyclopropyl, c-Pn: cyclopentyl, Bn: benzyl, NMR: nuclear magnetic resonance spectrum (TMS internal standard), MS: mass spectrometry, fumarate: fumaric acid, HC1 salt: hydrochloride, 2HC1 salt 2hydrochloride, free base: a free form [Table 2] [Table 3] [Table 4] [Table 5] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14] 196253/2

Claims

196253/5 A BIOMETRIC SENSOR AND A METHOD OF PERFORMING A BIOMETRIC FUNCTION CROSS-REFERENCES TO RELATED APPLICATIONS [0001 - 0006] This application is related to U.S. Pat. Appl. No. 09/874,740, entitled "APPARATUS AND METHOD OF BIOMETRIC DETERMINATION USING SPECIALIZED OPTICAL SPECTROSCOPY SYSTEM," filed June 5, 2001, and published as US 2002/0183624 Al. BACKGROUND OF THE INVENTION [0007] This application relates generally to biometrics. More specifically, this application relates to methods and systems for performing biometric measurements that use spectral information. [0008] "Biometrics" refers generally to the statistical analysis of characteristics of living bodies. One category of biometrics includes "biometric identification," which commonly operates under one of two modes to provide automatic identification of people or 1 196253/5 to verify purported identities of people. Biometric sensing technologies measure the physical features or behavioral characteristics of a person and compare those features to similar prerecorded measurements to determine whether there is a match. Physical features that are commonly used for biometric identification include faces, irises, hand geometry, vein structure, and fingerprint patterns, which is the most prevalent of all biometric-identification features. Current methods for analyzing collected fingerprints include optical, capacitive, radio-frequency, thermal, ultrasonic, and several other less common techniques. [0009] Most of the fingerprint-collection methods rely on measuring characteristics of the skin at or very near the surface of a finger. In particular, optical fingerprint readers typically rely on the presence or absence of a difference in the index of refraction between the sensor platen and the finger placed on it. When an air-filled valley of the fingerprint is above a particular location of the platen, total internal reflectance ("TIR") occurs in the platen because of the air-platen index difference. Alternatively, if skin of the proper index of refraction is in optical contact with the platen, then the TIR at this location is "frustrated," allowing light to traverse the platen-skin interface. A map of the differences in TIR across the region where the finger is touching the platen forms the basis for a conventional optical fingerprint reading. There are a number of optical arrangements used to detect this variation of the optical interface in both bright-field and dark-field optical arrangements. Commonly, a single, quasimonochromatic beam of light is used to perform this TIR-based measurement. [0010] There also exists non-TER optical fingerprint sensors. In most cases, these sensors rely on some arrangement of quasimonochromatic light to illuminate the front, sides, or back of a fingertip, causing the light to diffuse through the skin. The fingerprint image is formed due to the differences in light transmission across the skin-platen boundary for the ridge and valleys. The differences in optical transmission are due to changes in the Fresnel reflection characteristics due to the presence or absence of any intermediate air gap in the valleys, as known to one of familiarity in the art. [001 1 ] Optical fingerprint readers are particularly susceptible to image quality problems due to non-ideal conditions. If the skin is overly dry, the index match with the platen will be compromised, resulting in poor image contrast. Similarly, if the finger is very wet, the valleys may fill with water, causing an optical coupling to occur all across the fingerprint region and greatly reducing image contrast. Similar effects may occur if the pressure of the finger on the platen is too little or too great, the skin or sensor is dirty, the skin 2 1 96253/5 is aged and/or worn, or overly fine features are present such as may be the case for certain ethnic groups and in very young children. These effects decrease image quality and thereby decrease the overall performance of the fingerprint sensor. In some cases, commercial optical fingerprint readers incorporate a thin membrane of soft material such as silicone to help mitigate these effects aiid resiore performance. As a soft material, the membrane is subject lo damage, wear, and contamination, limiting the use of the sensor without maintenance. [0012] Optical Fingerprint readers, such as those based on TIR, as well as other modalities such as capacitance, RF, and others, typically produce images that are affected to some degree by the nonideal imaging conditions present during acquisition. An analysis of the textura] characteristics of the resulting images is thus affected by the sampling conditions, which may limit or obscure the ability to observe the textural characteristics of the person's skin. Tlie consequence of this is that texture is of limited utility in such sensing modalities. [0013) Biometric sensors, particularly fingerprint biometric sensors, are generally prone to being defeated by various forms of spoof samples. In the case of fingerprint readers, a variety of methods are known in the art for presenting readers with a fingerprint pattern of an authorized user that is embedded in some kind of inanimate material such as paper, gelatin, epoxy, latex, and the like. Thus, even if a fingerprint reader can be considered to reliably determine the presence or absence of a matcliing fingerprint pattern, it is also critical to the overall system security to ensure that the matching pattern is being acquired from a genuine, living finger, which may be difficult to ascertain with many common sensors. [0014] Another way in which some biometric systems may be defeated is through the use of a replay attack. In this scenario, an intruder records the signals coming from the sensor when an authorized user is using the system. At a later time, the intruder manipulates the sensor system such that the prerecorded authorized signals may be injected into the system, thereby bypassing the sensor itself and gaining access to the system secured by the biometric. 10015] A common approach to making biometric sensors more robust, more secure, and less error-prone is to combine sources.of biometric signals using an approach sometimes referred to in the art as using "dual," "combinatoric," "layered," "fused," "multibiometric," or "multifactor biometric" sensing. To provide enhanced security in this way, biometric technologies are combined in such a way that different technologies measure portions of the 3 1 96253/5 body at the same time and are resistant to being defeated by using different samples or techniques to defeat the different sensors that are combined. When technologies are combined in a way that they view the same part of the body the)' are referred to as being "tightly coupled." [0016] The accuracy of noninvasive optical measurements of physiological analytes such as glucose, alcohol, hemoglobin, urea, and cholesterol can be adversely affected by variation of the skin tissue. In some cases it is advantageous to measure one or more physiological analytes in conjunction with a biometric measurement. Such dual measurement has potential interes! and application to both commercial and law-enforcement markets. (0017] There is accordingly a general need in the art for improved methods and systems for biometric sensing and analyte estimation using multispectral imaging systems and methods. BRIEF SUMMARY OF THE INVENTION [0018J Embodiments of the invention provide methods and systems for performing biometric functions. Image-texture measures are used to enable texture biometrics in which biometric functions are performed through an analysis of texture characteristics of skin sites. [0019] Thus, in a first set of embodiments, a method is provided of performing a biometric function. A purported skin site of an individual is illuminated with illumination light. The purported skin site is in contact with a surface. Light scattered from the purported skin site is received substantially in a plane that includes the surface. An image is formed from the received light. An image-texture measure is generated from the image. The generated image-texture measure is analyzed to perform the biometric function, [0020] In certain embodiments, the biometric function comprises an antispoofing function; in such embodiments the image-texture measure is analyzed to determine whether the purported skin site comprises living tissue. In other embodiments, the biometric function comprises an identity function; in such embodiments, the image-texture measure is analyzed to determine an identity of the individual. In still other embodiments, the biometric function comprises a demographic or anthropometric function; in such embodiments, the image-texture measure is analyzed to estimate a demographic or anthropometric characteristic of the individual. 4 196253/5 [0021 | The surface may be the surface of an imaging detector, with light scattered from the purported skin site being received at the imaging detector. Alternatively, a pattern of light may be translated from the plane to an imaging detector disposed outside the plane without substantial degradation or attenuation of the pattern, with the translated pattern being received a! the imaging detector. In different embodiments, the light scattered from the purported skin site may be received at a monochromatic imaging detector or at a color imaging detector. |0022] In some embodiments, the illumination light is white light. The image may then comprise a plurality of images corresponding to different wavelengths. The image- texture measure may accordingly be generated by performing a spatial moving-window analysis of each of the plurality of images. For instance, moving-window Fourier transforms may be calculated on the plurality of images. Alternatively, a moving-window centrality measure and a moving-window variability measure of the plurality of images maybe calculated. (0023J In analyzing the generated image-texture measure to perform the biometric function, the generated image-texture measure may be compared with a reference image- texture measure. In some cases, the reference image-texture measure was generated from a reference image formed from light scattered from a reference skin site with the purported skin site being substantially different from the reference skin site, b certain embodiments, spectral features of the received light are compared with reference spectral features in performing the biometric function. [0024] b a second set of embodiments, a biometric sensor is provided. The sensor comprises a surface, an illumination subsystem, a detection subsystem, and a computational unit. The surface is adapted for contact with a purported skb site. The illumination subsystem is disposed to illuminate the purported skin site when the purported skb site is in contact with the surface. The detection subsystem is disposed to receive light scattered from the purported skb site, with the light being received substantially in a plane that bcludes the surface. The computational unit is interfaced with the detection subsystem and has instructions for forming an image from the received light. It also has instructions for generating an image-texture measure from the image and for analyzing the generated image-texture measure to perform the biometric function. 5 196253/5 J0025] There are a number of different biometric functions thai may be performed with such a sensor. In one embodiment, the biometric function comprises an antispoofing function, with the computational unit having instructions for determining whether the purported skin site comprises living tissue. In another embodiment, the biometric function comprises an identity function, with the computational unil having instructions for determining an identify of the individual from the generated image-texture measure. In still another embodiment, the biometric function comprises a demographic or anthropometric function, with the computational unit having instructions for estimating a demographic or anthropometric characteristic of the individual from the generated image-texture measure. {0026) In some instances, the biometric sensor further comprises an imaging detector. In one such embodiment, the surface is a surface of the imaging detector, with the detection subsystem comprising the imaging detector and being confi ured to receive light scattered from the purported skin site at the imaging detector. In another such embodiment, the imaging detector is disposed outside the plane. An optical arrangement is configured to translate a pattern of light from the plane to the imaging detector without substantial degradation or attenuation of the pattern. The detection system comprises the imaging detector and is configured to receive the translated pattern at the imaging detector. The imaging detector may comprise a monochromatic imaging detector or a color imaging detector in different embodiments. |l)027] In some cases, the illumination subsystem is configured to illuminate the purported skin site with white light. The image may then comprise a plurality of images corresponding to different wavelengths, with the instructions for generating the image-texture measure comprise instructions for performing a spatial moving-window analysis of each of the plurality of images. For instance, there may be instructions for calculating mo ing-window Fourier transforms on the plurality of images in one embodiment, while another embodiment has instructions for calculating a moving-window centrality measure and a moving-window variability measure of the plurality of images. |0028] In one embodiment, the instructions for analyzing the generated image-texture measure to perform the biometric function comprise instructions for comparing the generated image-texture measure with a reference image-texture measure. Such a reference image-texture measure may have been generated from a reference image formed from light scattered from a reference skin site, with the purported skin site being substantially different from the 6 196253/5 reference skin site. In a certain embodiment, the computational unit further has instructions for comparing spectral features of the received light with reference spectral features in performing the biometric function. [0029] Embodiments of the invention provide methods and systems for performing biometric functions. White light is used to illuminate a purported skin site and a color imager is used to collect light scattered from the purported skin site for the generation of multispectral data. These multispectral data may be generated in the form of multiple images of the skin site collected with different illumination wavelengths, which correspond to different volumes of illuminated tissue. These data are then subjected to different types of analyses depending on specific aspects of the biometric function to be performed. (0030] In a third set of embodiments, a biometric sensor is provided. A white-light illumination subsystem is disposed lo illuminate a purported skin site of an individual with white light. A detection subsystem is disposed to receive light scattered from the purported skin site and comprises a color imager on which the received light is incident. A computational unit is interfaced with the detection subsystem. The computational unit has instructions for deriving a plurality of spatially distributed images of the purported skin site from the received light with the color imager. The plurality of spatially distributed images correspond to different volumes of illuminated tissue of the individual. The computational unit also has instructions for analyzing the plurality of spatially distributed images to perform a biometric function. [0031 ] In one of these embodiments, the biometric function comprises an antispoofing function and the instructions for analyzing the plurality of spatially distributed images comprise instructions for determining whether the purported skin site comprises living tissue. In another of these embodiments, the instructions for analyzing the plurality of spatially distributed images to perform the biometric function comprise instructions for analyzing the plurality of spatially distributed images to estimate a demographic or anthropometric characteristic of the individual. In still another of these embodiments, the instructions for analyzing the plurality of spatially distributed images to perform the biometric function comprise instructions for analyzing the plurality of spatially distributed images to determine a concentration of an analyte in blood of the individual. [0032] In some embodiments, the biometric sensor may further comprise a platen in contact with the purported skin site, with the white-light illumination subsystem being 7 1 96253/5 adapted ιο illuminate the purported sldn site through the platen. In other embodiments, the white-light illumination subsystem may instead be adapted to illuminate the purported sldn site when the sldn site is not in physical contact with the biometric sensor. [0033] The white light may be provided in different ways in different embodiments. For example, in one embodiment, the white-light illumination subsystem comprises a broadband source of white light. In another embodiment, the white-light illumination subsystem comprises a plurality of narrow-band light sources and an optical arrangement to combine light provided by the plurality of narrow-band light sources, The plurality of narrow-band light sources may provide light at wavelengths that correspond to each of a set of primary colors. In some cases, the purported skin site and an illumination region where the purported skin site is illuminated are in relative motion. [0034] Some embodiments make use of polarization by including a first polarizing in the illumination system disposed to polarize the white light. The detection system then comprises a second polarizer disposed to encounter the received light. The first and second polarizers may be crossed relative to each other. In other embodiments, the first and second polarizers may be parallel, In some embodiments, the first polarizer may be omitted while retaining the second, in some embodiments, two or more of these polarization options may be combined in a single device. The detection system may also sometimes include an infrared filter disposed to encounter the received light before the received light is incident on the color imager. I003S] In certain instances, the purported skin site is a volar surface of a finger or hand and the biometric function comprises a biometric identification. The instructions for analyzing the plurality of spatially distributed images comprise instructions for deriving a surface fingerprint or palmprint image of the purported sldn site from the plurality of spatially distributed images. The surface fingerprint or palmprint image is then compared with a database of fingerprint or palmprint images to identify the individual. In other embodiment where the biometric function comprises a biometric identification, the instructions for analyzing the plurality of spatially distributed images instead comprise instructions for comparing the plurality of spatially distributed images with a database of multispectral images to identify the individual. (0036] In a fourth set of embodiments, a method is provided of performing a biometric function, A purported skin site of an individual is illuminated with white light. 8 196253/5 Light scattered from the purported skin site is received wiih a color imager on which the received light is incident. A plurality of spatially distributed images of the purported skin site are derived, with the plurality of spatially distributed images corresponding to different volumes of illuminated tissue of the individual. The plurality of spatially distributed images are analyzed to perform the biometric function. 10037) in some of these embodiments, the biometric function comprises an antispoofing function and analyzing the plurality of spatially distributed images comprises determining whether the purported skin site comprises living tissue. In other of these embodiments, the plurality of spatially distributed images are analyzed to estimate a demographic or anthropometric characteristic of the individual. In still different ones of these embodiments, the plurality of spatially distributed images are analyzed to determine a concentration of an analyte in blood of the individual. [0038] The purported skin site may sometimes be illuminated by directing the white light through a platen in contact with the purported skin site. In some instances, the purported skin site may be illuminated with a broadband source of white light, while in other instances a plurality of narrow-band beams, perhaps corresponding to a set of primary colors, may be generated and combined. The purported skin site might sometimes be in relative motion with an illumination region where the purported skin site is illuminated. (0039] In one embodiment the while light is polarized with a first polarization and the received light scattered from the purported skin site is polarized with a second polarization. The first and second polarizations may be substantially crossed relative to each other or may be substantially parallel to each other. The received light may sometimes be filtered at infrared wavelengths before the received light is incident on the color imager. [0040] In some instances, the biometric function comprises a biometric identification. For instance, the purported skin site could be a volar surface of a finger or hand. Analysis of the plurality of spatially distributed images could then proceed by deriving a surface fingerprint or palmprint image of the purported skin site from the plurality of spatially distributed images and comparing the surface fingerprint or palmprint image with a database of fingerprint or palmprint images. In an alternative embodiment, the plurality of spatially distributed images could be compared with a database of multispectrai images to identify the individual. 9 196253/5 BRIEF DESCRIPTION OF THE DRAWINGS [0041] A further understanding of the nature and advantages of the present invention may be realized by reference to the remaining portions of the specification and the drawings wherein like reference labels are used throughout the several drawings to refer to similar components. In some instances, reference labels include a numerical portion followed by a latin-letter suffix; reference to only the numerical portion of reference labels is intended to refer collectively to all reference labels that have that numerical portion but different latin- letter suffices. [0042] Fig. 1 provides a front view of a noncontact biometric sensor in one embodiment of the invention; [0043] Fig. 2A provides an illustration of a structure for a Bayer color filter array, which may be used in embodiments of the invention; [0044] Fig. 2B is a graph showing color response curves for a Bayer color filter array like that illustrated in Fig. 2 A; [0045] Fig. 3 provides a front view of a noncontact biometric sensor in another embodiment of the invention; [0046] Fig. 4 provides a top view of a sensor configuration that collects data during relative motion between a skin site and an optically active region of the sensor; [0047] Fig. 5 illustrates a multispectral datacube that may be used in certain embodiments of the invention; [0048] Fig. 6 is a front view of a contact biometric sensor in one embodiment of the invention; [0049] Fig. 7A provides a side view of a contact biometric sensor in an embodiment; [0050] Fig. 7B provides a side view of a contact biometric sensor in another embodiment; [0051] Fig, 8 provides a front view of a contact biometric sensor in a further embodiment of the invention; 10 1 96253/5 10052) Fig, 9A illustrates a structure for a contact texture biometric sensor in an embodiment of the invention; [0053] Fig. 9B provides a side view of a contact texture biometric sensor in one configuration; [0054] Fig. 9C provides a side view of a contact texture biometric sensor in another configuration; [0055] Fig. ] 0 is schematic representation of a computer system that may be used to manage functionality of contact and noncontact biometric sensors in accordance with embodiments of the invention; [0056] Fig. 1 1 is a flow diagram summarizing methods of using contact and noncontact biometric sensors and illustrates a number of different biometric functions that may be performed; and (00571 Fig. 12 is a flow diagram summarizing methods of operation of contact texture biometric sensors in accordance with embodiments of the invention. DETAILED DESCRIPTION OF THE INVENTION I . Overview [0058] Embodiments of the invention provide methods and systems that allow for the collection and processing of a variety of different types of biometric measurements, including integrated, multifactor biometric measurements in some embodiments. These measurements may provide strong assurance of a person's identity, as well as of the authenticity of the biometric sample being taken. In some embodiments, a sensor uses white light that penetrates the surface of the person's skin, and scatters within the skin and/or the underlying tissue. As used herein, "white light" refers to light that has a spectral composition amenable to separation into constituent wavelength bands, which in some cases may comprise primary colors. The usual primary colors used to define white light are red, green, and blue, but other combinations may be used in other instances, as will be known to those of skill in the art. For clarity, it is emphasized that "white light" as used herein might not appear white to a human observer and might have a distinct tint or color associated with it because of the exact 1 1 1 96253/5 wavelength distribution and intensity of the constituent wavelength bands. In other cases, the wliite light may comprise one or more bands in the ultraviolet or infrared spectral regions. In some cases, the white light mighl not even be visible at all lo a human observer when it consists of wavelength bands hi the infrared and/or ultraviolet spectral regions. A portion of the light scattered by the skin and/or underlying tissue exits the skin and is used to form an image of the structure of the tissue at and below the surface of the skin. Because of the wavelength-dependent properties of the skin, the image formed from each wavelength of light comprised by the white light may be different from images formed a! other wavelengths. Accordingly, embodiments of the invention collect images in such a way that characteristic spectral and spatial information may be extracted from the resulting image. [0059] In some applications, it may be desirable to estimate other parameters and characteristics of a body, either independently or in combination with a biometric measurement. For example, in one specific such embodiment, an ability is provided to measure analyte levels of a person simultaneously with measurement of a fingerprint pattern. Applications to law enforcement may be found in embodiments where the measure analyte comprises a blood-alcohol level of the person; such embodiments also enable a variety of commercial applications thai include restricting molor-vehicie access. In this way, the analyte measurement and the identity of the person on whom the measurement is made may be inextricably linked. [0060] Skin composition and structure is very distinct, very complex, and varies from person lo person. By performing optical measurements of the spatiospectral properties of skin and underlying tissue, a number of assessments may be made. For example, a biometric- identification function may be performed to identify or verify whose skin is being measured, a liveness function may be performed to assure that the sample being measured is live and viable skin and not another type of material, estimates may be made of a variety of physiological parameters such as age gender, ethnicity, and other demographic and anthropometric characteristics, and/or measurements may be made of the concentrations of various analytes and parameters including alcohol, glucose, degrees of blood perfusion and oxygenation, biliruben, cholesterol, urea, and the like. [0061] The complex structure of skin may be used in different embodiments to tailor aspects of the methods and systems for particular functions. The outermost layer of skin, the epidermis, is supported by the underlying dermis and hypodermis, The epidermis itself may 12 196253/5 have five identified sublayers that include the stratum corneum, the stratum lucidum, the stratum granulosum, the stratum spinosum, and the stratum germinativum. Thus, for example, the skin below the top-most stratum comeum has some characteristics that relate to the surface topography, as well as some characteristics that change with depth into the skin, While the blood supply to skin exists in the dermal layer, the dermis has protrusions into the epidermis known as "dermal papillae," which bring the blood supply close to the surface via capillaries. In the volar surfaces of the fingers, this capillary structure follows the pattern of the friction ridges and valleys on the surface. In some other locations on the body, the structure of the capillary bed may be less ordered, but is still characteristic of the particular location and person. As well, the topography of the interface between the different layers of skin is quite complex and characteristic of the skin location and the person. While these sources of subsurface structure of skin and underlying tissue represent a significant noise source for non-imaging optical measurements of skin for biometric determinations or analyte measurements, the structural differences are manifested by spatiospectral features that can be compared favorably through embodiments of the invention. (0062] In some instances, inks, dyes and/or other pigmentation may be present in portions of the skin as topical coating or subsurface tattoos. These forms of artificial pigmentation may or may not be visible to the naked human eye. However, if one or more wavelengths used by the apparatus of the present invention is sensitive to the pigment, the sensor can be used in some embodiments to verify the presence, quantity and/or shape of the pigment in addition to other desired measurement tasks. [0063] In general, embodiments of the present invention provide methods and systems that collect spatiospectral information that may be represented in a multidimensional data structure that has independent spatial and spectral dimensions. In certain instances, the desired information is contained in just a portion of the entire multidimensional data structure. For example, estimation of a uniformly distributed, spectrally active compound may require just the measured spectral characteristics, which may be extracted from the overall multidimensional data structure. In such cases, the overall system design may be simplified to reduce or eliminate the spatial component of the collected data by reducing the number of image pixels, even to a limit of a single pixel. Thus, while the systems and methods disclosed are generally described in the context of spatiospectral imaging, it will be recognized that the invention encompasses similar measurements in which the degree of imaging is greatly reduced, even to the point where there is a single detector el ement. 13 1 96253/5 2, Noncontacl Biometric Sensors [00i>4] One embodiment of the invention is depicted with the schematic diagram of Fig. 1 , which shows a front view of a noncontact biometric sensor 101. The sensor 101 comprises an illumination subsystem 121 having one or more light sources 103 and a detection subsystem 123 with an imager 1 15. The figure depicts an embodiment in which the illumination subsystem 121 comprises a plurality of illumination subsystems 121 a and 121b, but the invention is not limited by the number of illumination or detection subsystems 121 or 123. For example, the number of illumination subsystems 121 may conveniently be selected to achieve certain levels of illumination, to meet packaging requirements, and to meet other structural constraints of the sensor 101. Illumination light passes from the source 103 through illumination optics 105 that shape the illumination to a desired form, such as in the form of flood light, light lines, light points, and the like. The illumination optics 105 are shown for convenience as consisting of a lens bur may more generally include any combination of one or more lenses, one or more mirrors, and/or other optical elements. The illumination optics 105 may also comprise a scanner mechanism (not shown) to scan the illumination light in a specified one-dimensional or two-dimensional pattern, The light source 103 may comprise a point source, a line source, an area source, or may comprise a series of such sources in different embodiments. In one embodiment, the illumination light is provided as polarized light, such as by disposing a linear polarizer 107 through which the light passes before striking a finger 1 19 or other skin site of the person being studied. Embodiments like those shown in Fig. 1 are referred to herein as "noncontact" sensors because the imaged skin site may be positioned to interact with the light without being in contact with any solid surface. In "contact" biometric sensors described in detail below, the imaged skin site is in contact with some solid surface such as a platen or light detector, [0065J In some instances, the light source 103 comprises a white-light source, which may be provided as a broad-band source or as a collection of narrow-band emitters in different embodiments. Examples of broad-band sources include white-light emitting diodes ("LEDs"), incandescent bulbs or glowbars, and the like. Collections of narrow-band emitters may comprise quasimonochromatic light sources having primary-color wavelengths, such as 14 196253/5 in an embodiment that includes a red LED or laser diode, a green LED or laser diode, and a blue LED or laser diode. [0066] An alternative mechanism for reducing the directly reflected light makes use of optical polarizers. Both linear and circular polarizers can be employed advantageously to make the optical measurement more sensitive to certain skin depths, as known to one familiar with the art. In the embodiment illustrated in Fig. 1 , the illumination light is polarized by linear polarizer 107. The detection subsystem 123 may then also include a linear polarizer 1 J 1 that is arranged with its optical axis substantially orthogonal to the illumination polarizer 107. In this way, light from the sample must undergo multiple scattering events to significantly change it state of polarization. Such events occur when the light penetrates the surface of the skin and is scattered back to the detection subsystem 123 after many scatter events. [0067] Conversely, the use of two polarizers 107 and 1 1 1 may also be used to increase the influence of directly reflected light by arranging the polarizer 1 1 1 to be substantially parallel to polarizer 107. In some systems, it may be advantageous to combine two or more polarization configurations in a single device to enable the collection of multispectral data collected under two different polarization conditions (i.e. under crossed- polarization and under parallel-polarization conditions). In other embodiments, either polarizer 107 or U 1, or both, may be omitted, allowing for the collection of substantially randomly polarized light. [0068] The detection subsystem 123 may incorporate detection optics that comprise lenses, mirrors, phase plates and wavefront coding devices, and/or other optical elements that form an image onto the detector 1 15. The detection optics 1 13 may also comprise a scanning mechanism (not shown) to relay portions of the overall image onto the detector 1 15 in sequence. In all cases, the detection subsystem 123 is configured to be sensitive to light that has penetrated the surface of the skin and undergone optical scattering within the skin and/or underlying tissue before exiting the skin. [0069] In embodiments where white light is used, the detector 115 may comprise a Bayer color filter array in which filter elements corresponding to a set of primary colors are arranged in a Bayer pattern. An example of such a pattern is shown in Fig. 2A for an arrangement that uses red 204, green 212, and blue 208 color filter elements. In some instances, the detector subsystem 123 may additionally comprise an infrared filter 1 14 disposed to reduce the amount of infrared light detected. As seen from the color response 15 1 96253/5 curve for a typical Bayer filter array shown in Fig. 2B, there is generally some overlap in the spectral ranges of the red 224, green 232, and blue 228 transmission characteristics of the filter elements. As evident particularly in the curves for the green 232 and blue 228 transmission characteristics, the filter array may allow the transmission of infrared light. This is avoided with !he inclusion of an infrared filler 1 ] 4 as pan of the detector subsystem. In other embodiments, the infrared filter 1 14 may be omitted and one or more light sources 1 03 that emit infrared light may be incorporated, in this way, all color filter elements 204, 208, and 212 may allow the light to substantially pass through, resulting in an infrared image across the entire detector 115. [0070] Another embodiment of a noncontact biometric sensor is shown schematically with the front view of Fig. 3. In this embodiment, the biometric sensor 301 comprises an illumination subsystem 323 and a detection subsystem 325. Similar to the embodiment described in connection with Fig. 1 , there may be multiple illumination subsystems 323 in some embodiments, with Fig. 3 showing a specific embodiment having two illumination subsystems 323. A white-!ight source 303 comprised by the illumination subsystem 323 may be an)' source of white light, including the broad-band or combination of narrow-band sources described above. Light from the white-light source 303 passes through illumination optics 305 and a linear polarizer 307 before passing into the skin site 119. A portion of the light is diffusely reflected from the skin site 119 into the detection subsystem 325, which comprises imaging optics 315 and 319, a linear polarizer 31 1, and a dispersive optical element 313. The dispersive element 313 may comprise a one- or two-dimensional grating, which may be transmissive or reflective, a prism, or any other optical component known in the art to cause a deviation of the path of light as a function of the light's wavelength.- In the illustrated embodiment, the first imaging optics 319 acts to collimate light reflected from the skin site 1 19 for transmission through the linear polarizer 311 and dispersive element 313. Spectral components of the light are angularly separated by the dispersive element 313 and are separately focused by the second imaging optics 315 onto a detector. As discussed in connection with Fig. 1 , when the optical axis of the polarizers 307 and 311 are oriented to be substantially orthogonal to each other, polarizers 307 and 31 1 respectively comprised by the illumination and detection subsystems 323 and 325 act to reduce the detection of directly reflected light at the detector 317. The polarizers 307, 311 may also be oriented such that their optical axes are substantially parallel, which will increase the detection of directly 16 1 96253/5 reflected light at the detector 317. In some embodiments, either polarizer 307 or 31 1 , or both, may be o itted. [0071 ] The image generated from light recei ved at the detector is thus a "coded" image in the manner of a computer tomographic imaging spectrometer ("CTIS"). Both spectral and spatial information are simultaneously present in the resulting image. The individual spectral patterns may be obtained by mathematical inversion or "reconstruction" of the coded image. [0072] The description of the contact!ess sensor of Fig. 1 noted that a scanner mechanism may be provided to scan the illumination light. This is an example of a more general class of embodiments in which there is relative motion of the illumination region and skin site. In such embodiments, the image may be constructed by building up separate image portions collected during the relative motion. Such relative motion may also be achieved in embodiments that configure the sensor in a swipe configuration, in which the user is instructed to translate the skin site. One example of a swipe sensor is shown in top view with the schematic illustration of Fig. 4. In this figure, the illumination region 403 and detection region 405 of a sensor 401 are substantially collinear. In some embodiments of a swipe sensor 401 , there may be more than a single illumination region. For example, there may be a plurality of illumination regions arranged on either side of the detection region 405. In some embodiments, the illumination region 403 may partially or fully overlay the detection region. The image data are collected with the sensor by translating a finger or other body part through the optically active region, as indicated by the arrow in Fig. 4. A swipe sensor may be implemented with any of the contactless sensor configurations described above, although in some implementations it may be used with a contact configuration, examples of which are described in detail below. The light that is received sequentially from discrete portions of the skin site is used to build up the image that is subsequently used for biometric applications. [0073] The embodiments described above produce a body of spatio-spectral data, which may be used in biometrics applications as described below. The invention is not limited to any particular manner of storing or analyzing the body of spatio-spectral data. For purposes of illustration, it is shown in the form of a datacube in Fig. 5. The datacube 501 is shown decomposed along a spectral dimension with a plural ity of planes 503, 505, 507, 509, 51 1 , each of which corresponds to a different portion of the light spectrum and each of which includes spatial information. In some instances, the body of spatio-spectral data may include additional types of information beyond spatial and spectral information. For instance, different illumination 17 1 96253/5 conditions as defined by different illumination structures, different polarizations, and the like may provide additional dimensions of information. More broadly, data collected under a plurality of optical conditions, whether they be collected simultaneously or sequentially, is referred to herein as "multispectral" data. A more complete description of aspects of multispectral data is described in commonly assigned U.S. Pub. No. 2006/0244947, entitled "MULTISPECTRAL BIOMETRIC SENSORS". Spatio-spectral data may thus be considered to be a subset of certain types of multispectral data where the different optical conditions include different illumination wavelengths. [0074] In an embodiment where illumination takes place under white light, the images 503, 505, 507, 509, and 51 1 might correspond, for example, to images generated using light at 450 nm, 500 nm, 550 nm, 600 nm, and 650 nm. In another example, there may be three images that correspond to the amount of light in the red, green, and blue spectral bands at each pixel location. Each image represents the optical effects of light of a particular wavelength interacting with skin. Due to the optical properties of skin and skin components that vary by wavelength, each of the multispectral images 503, 505, 507, 509, and 51 1 will be, in general, different from the others. The datacube may thus be expressed as R(Xs, Ys> ¾ Υι> λ) and describes the amount of diffusely reflected light of wavelength λ seen at each image point Xj, Yj when illuminated at a source point X$, Ys-Different illumination configurations (flood, line, etc.) can be summarized by summing the point response over appropriate source point locations. A conventional non-TIR fingerprint image F(Xj, Yj) can loosely be described as the multispectral data cube for a given wavelength, λο, and summed over all source positions: Conversely, the spectral biometric dataset S(X) relates the measured light intensity for a given wavelength λ to the difference & between the illumination and detection locations: The datacube R is thus related to both conventional fingerprint images and to spectral biometric datasets. The datacube R is a superset of either of the other two data sets and 18 1 96253/5 contains correlations and other information that may be lost in either of the two separate modalities. [0075] The light that passes into the skin and/or underlying tissue is generally affected by different optical properties of the skin and/or underlying tissue at different wavelengths. Two optical effects in the skin and/or underlying tissue that are affected differently at different wavelengths are scatter and absorbance. Optical scatter in skin tissue is generally a smooth and relatively slowly varying function wavelength. Conversely, absorbance in skin is generally a strong function of wavelength due to particular absorbance features of certain components present in the skin. For example blood, melanin, water, carotene, biliruben, ethanol, and glucose all have significant absorbance properties in the spectral region from 400 nm to 2.5 μπι, which may sometimes be encompassed by the white-light sources. [0076] The combined effect of optical absorbance and scatter causes different illumination wavelengths to penetrate the skin to different depths. This effectively causes the different spectral images to have different and complementary information corresponding to different volumes of illuminated tissue. In particular, the capillary layers close to the surface of the skin have distinct spatial characteristics that can be imaged at wavelengths where blood is strongly absorbing. Because of the complex wavelength-dependent properties of skin and underlying tissue, the set of spectral values corresponding to a given image location has spectral characteristics that are well-defined and distinct. These spectral characteristics may be used to classify the collected image on a pixel-by-pixel basis. This assessment may be performed by generating typical tissue spectral qualities from a set of qualified images. For example, the spatio-spectral data shown in Fig. 5 may be reordered as an N x 5 matrix, where N is the number of image pixels that contain data from living tissue, rather than from a surrounding region of air. An eigenanalysis or other factor analysis performed on this set matrix produces the representative spectral features of these tissue pixels. The spectra of pixels in a later data set may then be compared to such previously established spectral features using metrics such as Mahalanobis distance and spectral residuals. If more than a small number of image pixels have spectral qualities that are inconsistent with living tissue, then the sample is deemed to be non-genuine and rejected, thus providing a mechanism for incorporating antispoofing methods in the sensor based on determinations of the liveness of the sample. 19 1 96253/5 |U077j Alternatively, textural characteristics of the skin may alone or in conj unction with the spectral characteristics be used to determine the authenticity of the sample. For example, each spectral image may be analyzed in such a way that the magnitude of various spatial characteristics may be described. Methods for doing so include wavelet transforms, Fourier transforms, cosine transforms, gray-level co-occurrence, and the like. The resulting coefficients from any such transform described an aspect of the texture of the image from which they were derived. The set of such coefficients derived from a set of spectral images thus results in a description of the chromatic textural characteristics of the multispectral data. These characteristics may then be compared to similar characteristics of known samples to perform a biometric determination such as spoof or liveness determination. Methods for performing such determinations are generally similar to the methods described for the spectral characteristics above. Applicable classification techniques for such determinations include linear and quadratic discriminant analysis, classification trees, neural networks, and other methods known to those familiar in the art. [0078] Similarly, in an embodiment where the sample is a volar surface of a hand or finger, the image pixels may be classified as "ridge," "valley," or "other" based on their spectra] qualities or their chromatic textural qualities. This classification can be performed using discriminant analysis methods such as linear discriminant analysis, quadratic discriminant analysis, principal component analysis, neural networks, and others known to those of skill in the art. Since ridge and valley pixels are contiguous on a typical volar surface, in some instances, data from the local neighborhood around the image pixel of interest are used to classify the image pixel. In this way, a conventional fingerprint image may be extracted for further processing and biometric assessment. The "other" category may indicate image pixels that have spectral qualities that are different than anticipated in a genuine sample. A threshold on the total number of pixels in an image classified as "other" may be set. If this threshold is exceeded, the sample may be determined to be non-genuine and appropriate indications made and actions taken. [0079] In a similar way, multispectral data collected from regions such as the volar sui'face of fingers may be analyzed to directly estimate the locations of "minutiae points," which are defined as the locations at which ridges end, bifurcate, or undergo other such topographic change. For example, the chromatic textural qualities of the multispectral dataset may be determined in the manner described above. These qualities may then be used to classify each image location as "ridge ending," "ridge bifurcation," or "other" in the manner 20 1 96253/5 described previously. In this way, minutiae feature extraction may be accomplished directly from the multispectral data without having to perform computationally laborious calculations such as image normalization, image binarization, image thinning, and minutiae filtering, techniques that are known to those familiar in the art. [0080] Biometric determinations of identity may be made using the entire body of spatio-spectral data or using particular portions thereof. For example, appropriate spatial filters may be applied to separate out the lower spatial frequency information that is typically representative of deeper spectrally active structures in the tissue. The fingerprint data may be extracted using similar spatial frequency separation and/or the pixel-classification methods disclosed above. The spectral information can be separated from the active portion of the image in the manner discussed above. These three portions of the body of spatio-spectral data may then be processed and compared to the corresponding enrollment data using methods known to one familiar in the art to determine the degree of match. Based upon the strength of match of these characteristics, a decision can be made regarding the match of the sample with the enrolled data. Additional details regarding certain types of spatio-spectral analyses that may be performed are provided in U.S. Pat. Appl. Pub. No. 2004/0240712 Al, entitled "MULTISPECTRAL BIOMETRIC SENSOR". [0081] As previously noted, certain substances that may be present in the skin and underlying tissue have distinct absorbance characteristics. For example, ethanol has characteristic absorbance peaks at approximately 2.26 μπι, 2.30 μπι, and 2.35 μπι, and spectral troughs at 2.23 μπι, 2.28 μπι, 2.32 μπι, and 2.38 μπι. In some embodiments, noninvasive optical measurements are performed at wavelengths in the range of 2.1 - 2.5 μπι, more particularly in the range of 2.2 - 2.4 μπι. In an embodiment that includes at least one of the peak wavelengths and one of the trough wavelengths, the resulting spectral data are analyzed using multivariate techniques such as partial least squares, principal-component regression, and others known to those of skill in the art, to provide an estimate of the concentration of alcohol in the tissue, as well as to provide a biometric signature of the person being tested. While a correlation to blood-alcohol level may be made with values determined for a subset of these wavelengths, it is preferable to test at least the three spectral peak values, with more accurate results being obtained when the seven spectral peak and trough values are measured. 21 1 96253/5 | 082] In other embodiments, noninvasive optica] measurements are performed al wavelengths in the range of 1 .5 - 1 ,9 μιη, more particularly in the range of 1.6 - 1 .8 μηι. In specific embodiments, optical measurements are performed at one or more wavelengths of approximately 1.67 μιιι, 1.69 μπι, 1.71 μτη, 1 .73 μηι, 1.74 μηι 1.76 μηι and 1 .78 μηι. The presence of alcohol is characterized at these wavelengths by spectral peaks al 1 .69 μιη, 1 .73 μπι, and 1.76 μπι and by spectral troughs at 1.67 μιη, 1.71 μιη, 1 .74 μτη, and 1 .78 μιη. Similar to the 2.1 - 2.5 μηι wavelength range, the concentration of alcohol is characterized b relative strengths of one or more of the spectra] peak and trough values. Also, while a correlation to blood-alcohol level may be made with values determined for a subset of these wavelengths in the 1.5 - 1.9 μιη range, it is preferable to test at least the three spectral peak values, with more accurate results being obtained when the seven spectral peak and trough values are measured. [0083] A small spectral alcohol-monitoring device may be embedded in a variety of systems and applications in certain embodiments. The spectral alcohol-monitoring device can be configured as a dedicated system such as may be provided to law-enforcement personnel, or may be integrated as part of an electronic device such as an electronic fob, wnstwatch, cellular telephone, PDA, or any other electronic device, for an individual 's personal use. Such devices may include mechanisms for indicating to an individual whether his blood- alcohol level is within defined Umits. For instance, the device may include red and green LEDs, with electronics in the device illuminating the green LED if the individual 's blood-alcohol level is within defined limits and illuminating the red LED if it is not. In one embodiment, the alcohol-monitoring device may be included in a motor vehicle, typically positioned so that an individual may conveniently place tissue, such as a fingertip, on the device. While in some instances, the device may function only as an informational guide indicating acceptability to drive, in other instances ignition of the motor vehicle may affirmatively depend on there being a determination that the individual has a blood-alcohol level less than a prescribed level. 3. Contact Biometric Sensors [0084] Biometric sensors may be constructed in a fashion similar' to that shown in Figs. 1 and 3, but configured so that the skin site is placed in contact with a platen. Such designs have certain additional characteristics that result from the interaction of light with the 22 1 96253/5 platen, sometimes permitting additional information to be incorporated as part of the collect spatio-spectral data. [0085] One embodiment is shown in Fig. 6, which provides a front view of a contact biometric sensor 601. Like the sensor illustrated in Fig. 1, the contact sensor 601 has one or more illumination subsystems 621 and a detection subsystem 623. Each of the illumination subsystems 621 comprises one or more white-light sources 603 and illumination optics that shape the light provided by the sources 603 into a desired form. As with the non-contact arrangements, the illumination optics may generally include any combination of optical elements and may sometimes include a scanner mechanism. In some instances, the illumination light is provided as polarized light by disposing a polarizer 607 through which the illumination light passes. Examples of white-light sources 603, including broad- and narrow-band sources were described above, and the sources 603 may be configured to provide sources having different shapes in different embodiments. [0086] The illumination light is directed by the illumination optics 621 to pass through a platen 617 and illuminate the skin site 119. The sensor layout 601 and components may advantageously be selected to minimize the direct reflection of the illumination optics 621. In one embodiment, such direct reflections are reduced by relatively orienting the illumination subsystem 621 and detection subsystem 623 such that the amount of directly reflected light detected is minimized. For instance, optical axes of the illumination subsystem 621 and the detection subsystem 623 may be placed at angles such that a mirror placed on the platen 617 does not direct an appreciable amount of illumination light into the detection subsystem 623. In addition, the optical axes of the illumination and detection subsystems 621 and 623 may be placed at angles relative to the platen 617 such that the angular acceptance of both subsystems is less than the critical angle of the system 601; such a configuration avoids appreciable effects due to total internal reflectance between the platen 617 and the skin site 119. [0087] The presence of the platen 617 does not adversely interfere with the ability to reduce the directly reflected light by use of polarizers. The detection subsystem 623 may include a polarizer 611 having an optical axis substantially orthogonal or parallel to the polarizer 607 comprised by the illumination subsystem 621. Surface reflections at the interface between the platen 617 and the skin site 119 are reduced in the case where polarizers 611 and 607 are oriented substantially orthogonal to each other since light from the 23 1 96253/5 sample must undergo sufficiently many scattering events to change its state of polarization before it can be sensed by the detector 615. The detection subsystem 623 may additionally incorporate detection optics that form an image of the region near the platen surface 617 onto the detector 615. In one embodiment, the detection optics 613 comprise a scanning mechanism (not shown) to relay portions of the platen region onto the detector 615 in sequence. An infrared filter 614 may be included to reduce the amount of infrared light detected, particularly in embodiments where the detector 615 is sensitive to infrared light, such as when a Bayer filter array is used. Conversely, as described above, the infrared filter 614 may be omitted in some embodiments and an additional light source 603 with emissions in the infrared may be included in some embodiments. [0088] As in the other arrangements described above, the detection subsystem 623 is generally configured to be sensitive to light that has penetrated the surface of the skin and undergone optical scattering within the skin and/or underlying tissue. The polarizers may sometimes be used to create or accentuate the surface features. For instance, if the illumination light is polarized in a direction parallel ("P") with the platen 617, and the detection subsystem 623 incorporates a polarizer 61 1 in a perpendicular orientation ("S"), then the reflected light is blocked by as much as the extinction ratio of the polarizer pair. However, light that crosses into the skin site at a ridge point is optically scattered, which effectively randomizes the polarization (though the skin does have some characteristic polarization qualities of its own, as is known to those of skill in the art). This allows a portion, on the order of 50%, of the absorbed and re-emitted light to be observed by the S-polarized imaging system. [0089] A side view of one of the embodiments of the invention is shown with the schematic drawing provided in Fig. 7A. For clarity, this view does not show the detection subsystem, but does show an illumination subsystem 621 explicitly. The illumination subsystem 621 in this embodiment has a plurality of white-light sources 703 that are distributed spatially. As shown in the drawing, the illumination optics 621 are configured to provide flood illumination, but in alternative embodiments could be arranged to provide line, point, or other patterned illumination by incorporation of cylindrical optics, focusing optics, or other optical components as known to those knowledgeable in the art. [0090] The array of white-light sources 703 in Fig. 7A need not actually be planar as shown in the drawing. For example, in other embodiments, optical fibers, fiber bundles, or 24 1 96253/5 fiber optical faceplates or tapers could convey the light from the light sources at sonic convenient locations to an illumination plane, where light is reimaged onto the skin site 1 19. The light sources could be controlled turning the drive currents on and off as LEDs might be. Alternatively, if an incandescent source is used, switching of the light may be accomplished using some form of spatial light modulator such as a liquid crystal modulator or using microelectromechanical-systems ("MEMS") technology to control apertures, min ors, or other such optical elements. Such configurations may allow the structure of the sensor to be simplified. One embodiment is illustrated in Fig. 7B, which shows the use of optical fibers and electronic scanning of illumination sources such as LEDs. Individual fibers 716a connect each of the LEDs located at an illumination array 71 0 to an imaging surface, and other fibers 716b relay the reflected light back to the imaging device 712, which may comprise a photodiode array, CMOS array, or CCD array. The set of fibers 716a and 71 b thus defines an optical fiber bundle 714 used in relaying light. [0091] Another embodiment of a contact biometric sensor is shown schematically with the front view of Fig. 8. In this embodiment, the biometric sensor 801 comprises one or more white-light illumination subsystems 823 and a detection subsystem 825. The illumination subsystems 823 comprise a white-light source 803 that provides light that passes through illumination optics 805 and a polarizer 807 to be directed to a platen 81 7 over which a skin site is disposed 1 19. A portion of the light is diffusely reflected from the skin site 1 19 into the detection subsystem 825, which comprises imaging optics 815 and 819, a crossed polarizer 81 1 , and a dispersive, optical element 813. The first imaging optics 81.9 collimate light reflected from the skin site 119 for transmission through the crossed polarizer 81 1 arid dispersive element 813. Separated spectral components are separately focused onto the detector 817 by the second imaging optics 815. [0092] Contact biometric sensors like those illustrated in Figs. 6 - 8 are also amenable to configurations in which the illumination region is in relative motion with the skin site. As previously noted, such relative motion may be implemented with a mechanism for scanning the illumination light and/or by moving the skin site. The presence of a platen in contact-sensor embodiments generally facilitates motion of the skin site by confining a surface of the skin site to a defined plane; in embodiments where freedom of motion is permitted in three dimensions, additional difficulties may result from movement of the skin site outside the imaging depth. A swipe sensor may accordingly be implemented with contact biometric sensors in a fashion as generally described in connection with Fig. 4 above, 25 1 96253/5 but with a platen that prevents motion of the skin site in one direction. While in some embodiments, the swipe sensor may be a stationary system, a contact configuration allows a roller system to be implemented in which the skin site is rolled over a roller structure that is transparent to the white light. An encoder may record position information and aid in stitching a full two-dimensional image from a resulting series of image slices, as understood by those of skill in the art. Light received from discrete portions of the skin site is used to build up the image. [0093] While the above descriptions of noncontact and contact biometric sensors have focused on embodiments in which white light is used, other embodiments may make use of other spectral combinations of light in similar structural arrangements. In addition, other embodiments may include additional variations in optical conditions to provide multispectral conditions. Some description of such multispectral applications is provided in commonly assigned U.S. Pat. Appl. Pub. No. 2004/0240712 Al, entitled "MULTISPECTRAL BIOMETRIC SENSOR," by Robert K. Rowe et al ; U.S. Pat. Application Publication No. 2006/0002597 Al, entitled "LIVENESS SENSOR," by Robert K. Rowe; U.S. Pat. Application Publication No. 2006/0062438 Al by Robert K. Rowe; U.S. Pat. Application Publication No. 2005/0271258 Al, entitled "MULTISPECTRAL IMAGING BIOMETRICS," by Robert K. Rowe; U.S. Pat. Appl. Pub. No. 2005/0265586 Al, entitled "MULTISPECTRAL BIOMETRIC IMAGING"; U.S. Pat. Appl. Pub. No. 2005/0265585 Al, entitled "MULTISPECTRAL LIVENESS DETERMINATION"; U.S. Pat. Appl. Pub. No. 2006/0244947 Al, entitled "MULTISPECTRAL BIOMETRIC SENSORS," by Robert K. Rowe. [0094] The noncontact and contact biometric sensors described above use white-light imaging in certain embodiments. The use of white light permits images to be collected simultaneously at multiple colors, with the overall speed of data collection being faster than in embodiments where discrete states are collected separately. This reduced data-collection 26 1 96253/5 time leads to a reduction in motion artifacts as the skin site moves during data collection. The overall sensor size may also be reduced and provided at lower cost by using a smaller number of light sources when compared with the use of discrete illumination sources for different colors. Corresponding reductions are also possible in the electronics used to support coordinated operation of the light sources. In addition, color imagers are currently available at prices that are typically lower than monochrome imagers. [0095] The use of white- light imaging also permits a reduction in data volume when the sensor is designed to use all pixels in achieving the desired resolution. For instance, a typical design criterion may provide a 1 -inch field with a 500 dots-per-inch resolution. This can be achieved with a monochrome camera having 500 x500 pixels. It can also be achieved with a 1000 x 1000 color camera when extracting each color plane separately. The same resolution can be achieved by using a 500 x 500 color imager and converting to {R, G, B} triplets and then extracting the monochrome portion of the image. This is a specific example of a more general procedure in which a color imager is used by converting to primary-color triplets, followed by extraction of a monochrome portion of an image. Such a procedure generally permits a desired resolution to be achieved more efficiently than with other extraction techniques. 4. Texture Biometric Sensor [0096] Another form of contact biometric sensor provided in embodiments of the invention is a texture biometric sensor. "Image texture" refers generally to any of a large number of metrics that describe some aspect of a spatial distribution of tonal characteristics of an image, some of which were described above. For example, some textures, such as those commonly found in fingerprint patterns or wood grain, are flowlike and may be well described by metrics such as an orientation and coherence. For textures that have a spatial regularity (at least locally), certain characteristics of the Fourier transform and the associated power spectrum are important such as energy compactness, dominant frequencies and orientations, etc. Certain statistical moments such as mean, variance, skew, and kurtosis may be used to describe texture. Moment invariants may be used, which are combinations of various moments that are invariant to changes in scale, rotation, and other perturbations. Gray-tone spatial dependence matrices may be generated and analyzed to describe image 27 196253/5 texture. The entropy over an image region may be calculated as a measure of image texture. Various types of wavelet transforms may be used to describe aspects of the image texture. Steerable pyramids, Gabor filters, and other mechanisms of using spatially bounded basis functions may be used to describe the image texture. These and other such measures of texture known to one familiar in the art may be used individually or in combination in embodiments of the invention. [0097] Image texture may thus be manifested by variations in pixel intensities across an image, which may be used in embodiments of the invention to perform biometric functions. In some embodiments, additional information may be extracted when such textural analysis is performed for different spectral images extracted from a multispectral data set, producing a chromatic textural description of the skin site. These embodiments advantageously enable biometric functions to be performed by capturing a portion of an image of a skin site. The texture characteristics of the skin site are expected to be approximately consistent over the skin site, permitting biometric functions to be performed with measurements made at different portions of the image site. In many instances, it is not even required that the portions of the skin site used in different measurements overlap with each other. [0098] This ability to use different portions of the skin site provides considerable flexibility in the structural designs that may be used. This is, in part, a consequence of the fact that biometric matching may be performed statistically instead of requiring a match to a deterministic spatial pattern. The sensor may be configured in a compact manner because it need not acquire an image over a specified spatial area. The ability to provide a small sensor also permits the sensor to be made more economically than sensors that need to collect complete spatial information to perform a biometric function. In different embodiments, biometric functions may be performed with purely spectral information, while in other embodiments, spatio-spectral information is used. [0099] One example of a structure for a texture biometric sensor is shown schematically in Fig. 9 A. The sensor 900 comprises a plurality of light sources 904 and an imager 908. In some embodiments, the light sources 904 comprise white-light sources, although in other embodiments, the light sources comprise quasimonochromatic sources. Similarly, the imager 908 may comprise a monochromatic or color imager, one example of which is an imager having a Bayer pattern. The sensor 900 is referred to herein as a 28 196253/5 "contact" sensor because the image is collected substantial!)' in the plane of the skin site 1 19 being measured. It is possible, however, to have different configurations for operating the sensor, some with the imager 908 substantially in contact with the skin site 1 19 and some with the imager 908 displaced from the plane of the skin site 1 19. [0100] This is shown for two illustrative embodiments in Figs. 9B and 9C. In the embodiment of Fig. 9B, the imager 908 is substantially in contact with the skin site 1 19. Light from the sources 904 propagates beneath the tissue of the skin site 1 19, permitting light scattered from the skin site 1 1 and in the underlying tissue to be detected by the imager 908. An alternative embodiment in which the imager 908 is displaced from the skin site 1 19 is shown schematically in Fig. 9C. In this drawing the sensor 900' includes an optical arrangement 912 that translates an image at the plane of the skin site 119 to the imager could comprise a plurality of optical fibers, which translate individual pixels of an image by total internal reflection along the fiber without substantially loss of intensity. In this way, the light pattern detected by the imager 908 is substantially the same as the light pattern formed at the plane of the skin site 1 19. The sensor 900' may thus operate in substantially the same fashion as the sensor 900 shown in Fig. 9B. That is, light from the sources 904 is propagated to the skin site, where it is reflected and scattered by underlying tissue after penetrating the skin site 119. Because information is merely translated substantially without loss, the image formed by the imager 908 in such an embodiment is substantially identical to the image that would be formed with an arrangement like that in Fig. 9 A. [0101] In embodiments where purely spectral information is used to perform a biometric function, spectral characteristics in the received data are identified and compared with an enrollment database of spectra. The resultant tissue spectrum of a particular individual includes unique spectral features and combinations of spectral features that can be used to identify individuals once a device has been trained to extract the relevant spectral features. Extraction of relevant spectral features may be performed with a number of different techniques, including discriminant analysis techniques. While not readily apparent in visual analysis of a spectral output, such analytical techniques can repeatably extract unique features that can be discriminated to perform a biometric function. Examples of specific techniques are disclosed in commonly assigned U.S. Pat. No. 6,560,352, entitled "APPARATUS AND METHOD OF BIOMETRIC IDENTIFICATION AND VERIFICATION OF INDIVIDUALS USING OPTICAL SPECTROSCOPY"; U.S. Pat. No. 6,816,605, entitled "METHODS AND SYSTEMS FOR BIOMETRIC IDENTIFICATION 29 1 96253/5 OF INDIVIDUALS USING LINEAR OPTICAL SPECTROSCOPY"; U.S. Pat. No. 6,628,809, entitled "APPARATUS AND METHOD FOR IDENTIFICATION OF INDIVIDUALS BY NEAR-INFRARED SPECTROSCOPY"; U.S. Pat. Appl. Pub. No. 2004/0047493 Al, entitled "APPARATUS AND METHOD FOR IDENTIFICATION OF INDIVIDUAL BY NEAR-INFRARED SPECTROSCOPY," by Robert K. Rowe et al; and U.S. Pat. Appl. Pub. No. 2002/0183624 Al, entitled "APPARATUS AND METHOD OF BIOMETRIC DETERMINATION USING SPECIALIZED OPTICAL SPECTROSCOPY SYSTEM," by Robert K. Rowe et al [0102] The ability to perform biometric functions with image-texture information, including biometric identifications, may exploit the fact that a significant portion of the signal from a living body is due to capillary blood. For example, when the skin site 119 comprises a finger, a known physiological characteristic is that the capillaries in the finger follow the pattern of the external fingerprint ridge structure. Therefore, the contrast of the fingerprint features relative to the illumination wavelength is related to the spectral features of blood. In particular, the contrast of images taken with wavelengths longer than about 580 nm are significantly reduced relative to those images taken with wavelengths less than about 580 nm. Fingerprint patterns generated with nonblood pigments and other optical effects such as Fresnel reflectance have a different spectral contrast. [0103] Light scattered from a skin site 119 may be subjected to variety of different types of comparative texture analyses in different embodiments. Some embodiments make use of a form of moving-window analysis of image data derived from the collected light to generate a figure of merit, and thereby evaluate the measure of texture or figure of merit. In some embodiments, the moving window operation may be replaced with a block-by-block or tiled analysis. In some embodiments, a single region of the image or the whole image may be analyzed at one time. [0104] In one embodiment, fast-Fourier transforms are performed on one or more regions of the image data. An in-band contrast figure of merit C is generated in such embodiments as the ratio of the average or DC power to in-band power. Specifically, for an index i that corresponds to one of a plurality of wavelengths comprised by the white light, the contrast figure of merit is 30 1 96253/5 In this expression, Γ:(ξ, η) is the Fourier transform of the image ./" (-v, v) at the wavelength corresponding to index i, where x and y are spatial coordinates for the image. The range defined by R\ow and ¾,„,, represents a limit on spatial frequencies of interest for fingerprint features. For example, R\ov/ may be approximate])' 1 .5 fringes/mm in one embodiment and ?hiph may be 3.0 fringes/mm. In an alternative formulation, the contrast figure of merit may be defined as the ratio of the integrated power in two different spatial frequency bands. The equation shown above is a specific case where one of the bands comprises only the DC spatial frequency. [0105] In another embodiment, moving-window means and moving-window standard deviations are calculated for the collected body of data and used to generate the figure of merit. In this embodiment, for each wavelength corresponding to index i, the moving- window mean μ/ and the moving-window standard deviation ov are calculated from the collected image (x, y). The moving windows for each calculation may be the same size and may conveniently be chosen to span on the order of 2— 3 fingerprint ridges. Preferably, the window size is sufficiently large to remove the fingerprint features but sufficiently smal l to have background variations persist. The figure of merit C, in this embodiment is calculated as the ratio of the moving-window standard deviation to the moving-window mean: [0106] In still another embodiment, a similar process is performed but a moving-window range {i.e., maxrimage values) - min(image values) ) is used instead of a moving-window standard deviation. Thus, similar to the previous embodiment, a moving-window mean u/ and a moving-window range δ; are calculated from the collected image f^x, y) for each wavelength corresponding to index i. The window size for calculation of the moving-window mean is again preferably large enough to remove the fingerprint features but small enough to maintain background variations. In some instances, the window size for calculation of the moving-window mean is the same as for calculation of the moving- window range, a suitable value in one embodiment spanning on the order of 2 - 3 fingerprint ridges. The figure of merit in this embodiment is calculated as the ratio of the moving-window mean: 31 1 96253/5 [0107] This embodimeni and the preceding one may be considered to be. specific cases of a more general embodiment in which moving-window calculations are performed on the collected data to calculate a moving-window certtrality measure and a moving-window variability measure. The specific embodiments illustrate cases in which the centrality measure comprises an unweighted mean, but may more generally comprise an}' other type of statistical centrality measure such as a weighted mean or median in certain embodiments. Similarly, the specific embodiments illustrate cases in which the variability measure comprises a standard deviation or a range, but may more generally comprise any other type of statistical variability measure such as a median absolute deviation or standard error of the mean in certain embodiments. [0108] In another embodiment that does not use explicit moving-window analysis, a wavelet analysis may be performed on each of the spectral images. In some embodiments, the wavelet analysis ma}' be performed in a way that the resulting coefficients are approximately spatially invariant. This may be accomplished by performing an undecimatcd wavelet decomposition, applying a dual-tree complex wavelet method, or other methods of the sort. Gabor filters, steerable pyramids and other decompositions of the sort may also be applied to produce similar coefficients. Whatever method of decomposition is chosen, the result is a collection of coefficients that are proportional to the magnitude of the variation corresponding to a particular basis function at a particular position on the image. To perform spoof detection, the wavelet coefficients, or some derived siurrrnary thereof, may be compared to the coefficients expected for genuine samples. If the comparison shows that the results are sufficiently close, the sample is deemed authentic. Otherwise, the sample is determined to be a spoof. In a similar manner, the coefficients may also be used for biometric verification by comparing the currently measured set of coefficients to a previously recorded set from the reputedly same person. 5. Exemplary Appli cations [0109] hi various embodiments, a biometric sensor, whether it be a noncontact, contact, or texture sensor of any of the types described above, may be operated by a 32 1 96253/5 computational .system to implement biornctric functionality. Fig. 10 broadly illustrates how individual system elements may be implemented in a separated or more integrated manner. The computational device 1000 is shown comprised of hardware elements that are electrical ! coupled via bus 1026, which is also coupled with the biometric sensor 1056. The hardware elements include a processor 1002, an input device 1 04, an output device 1006, a storage device 1008, a computer-readable storage media reader 1010a, a communications system 1014, a processing acceleration unit 101 6 such as a DSP or special-purpose processor, and a memory 1018. The computer-readable storage media reader 1010a is further connected to a computer-readable storage medium 101 0b, the combination comprehensively representing remote, local, fixed, and/or removable storage devices plus storage media for temporarily and/or more permanently containing computer-readable information. The communications system 1014 may comprise a wired, wireless, modem, and/or other type of interfacing connection and permits data to be exchanged with external devices. [0110] The computational device 1000 also comprises software elements, shown as being currently located within working memory 1020, including an operating system 1024 and other code 1022, such as a program designed to implement methods of the invention. It will be apparent to those skilled in the art that substantial variations may be used in accordance with specific requirements. For example, customized hardware might also be used and/or particular elements might be implemented in hardware, software (including portable software, such as applets), or both. Further, connection to other computing devices such as network input/output devices may be employed [011 J] An overview of functionality that may be implemented with the computational device are summarized with the flow diagram of Fig. 11. hi some embodiments, a purported skin site is illuminated as indicated at block 1 104 with white light. This permits the biometric sensor to receive light from the purported skin site at block 1 1 08. As described above, the received light may be analyzed in a number of different ways in implementing a biometric function. The flow diagram shows how certain combinations of analyses may be used in implementing the biometric function, although it is not necessary that all steps be performed, hi other instances, a subset of the steps may be perfomied, additional steps might be performed, and/or the indicated steps might be performed in a different order than indicated. 33 196253/5 |01 12J Ai block 1 1 12, a Iiveness check may be performed with the received light to confirm that the purported skin site is not some type of spoof, usually by verifying that it has the characteristics of living tissue. If a spoof is detecied, an alert may be issued at block 1 164. The specific type of alert that is issued may depend on the environment in which the biometric sensor is deployed, with audible or visual alerts sometimes being issued near the sensor itself; in other instances, silent alerts may be transmitted to security or law- enforcement personnel. [0113] The light received scattered from the purported skin site may be used at block 1 120 to derive a surface image of the purported skin site. In instances where the purported skin site is a volar surface of a finger, such a surface image will include a representation of the pattern of ridges and valleys on the finger, pcnnitting it to be compared with a database of conventional fingerprints at block 1 124. In addition or alternative! y, the received light may be used to derive a spatio-spectral image at block 1 12S. This image may be compared with a spatio-spectral database having images that are associated with individuals at block 1 132. In either instance, the comparison may permit the individual to be identified at block 1 136 as a result of the comparison. It is generally expected that higher-reliability identifications may be made by using the full spatio-spectral information to provide a comparison wi th spatio- spectral images. But in some applications, there may be greater availability of conventional fingerprint data, with some individuals having their fingerprints stored in large law- enforcement fingerprint databases but not in spatio-spectral databases. In such cases, embodiments of the invention advantageously permit the extraction of a conventional fingerprint image to perform the identification. [011 ] The spatio-spectral data includes still additional information that may provide greater confidence in the identification, whether the identification is made by comparison with a conventional fingerprint database or through comparison with spatio-spectral information. For example, as indicated at block 1 140, demographic and/or anthropometric characteristics may be estimated from the received light. When the database entry matched to the image at block 1 136 includes demographic or anthropometric information, a consistency check may be performed at block 1 144. For instance, an individual presenting himself may be identified as a white male having an age of 20 - 35 years from the estimated demographic and anthropometric characteristics. If the database entry against which the image is matched identifies the individual as a 68-year-old black woman, there is a clear inconsistency that would trigger the issuance of an alarm at block 1 1 64. 34 CLAIMS

1. A method of performing a biometric function, the method comprising: illuminating a purported skin site of an individual with illumination light having a plurality of wavelengths, wherein the purported skin site is in contact with a surface; receiving light scattered from the purported skin site, wherein the light is received substantially in a plane that includes the surface; using a processor to carry out the steps of: forming a plurality of images corresponding to different of the plurality of wavelengths from the received light; generating an image-texture measure from the plurality of images; and analyzing the generated image-texture measure to perform the biometric function.

2. The method recited in claim 1 wherein the biometric function comprises an antispoofing function and analyzing the generated image-texture measure comprises determining whether the purported skin site comprises living tissue from the generated image-texture measure.

3. The method recited in claim 1 wherein the biometric function comprises an identity function and analyzing the generated image-texture measure comprises determining an identity of the individual from the generated image-texture measure.

4. The method recited in claim 1 wherein the biometric function comprises a demographic or anthropometric function and analyzing the generated image-texture measure comprises estimating a demographic or anthropometric characteristic of the individual from the generated image-texture measure.

5. The method recited in claim 1 wherein: the surface is a surface of an imaging detector; and 36 1 96253/3 receiving light scattered from the purported skin site comprises receiving light scattered from the purported skin site at the imaging detector.

6. The method recited in claim 1 wherein receiving light scattered from the purported skin site comprises: translating a pattern of light from the plane to an imaging detector disposed outside the plane without substantial degradation or attenuation of the pattern; and receiving the translated pattern at the imaging detector.

7. The method recited in claim 1 wherein the illumination light is white light.

8. The method recited in claim 1 wherein generating the image-texture measure comprises performing a spatial moving-window analysis of each of the plurality of images.

9. The method recited in claim 8 wherein performing the spatial moving-window analysis comprises calculating moving-window Fourier transforms on the plurality of images.

10. The method recited in claim 8 wherein performing the spatial moving-window analysis comprises calculating a moving-window centrality measure and a moving-window variability measure of the plurality of images.

11. The method recited in claim 1 wherein receiving light scattered from the purported skin site comprises receiving light scattered from the purported skin site at a monochromatic imaging detector.

12. The method recited in claim 1 wherein receiving light scattered from the purported skin site comprises receiving light scattered from the purported skin site at a color imaging detector. 37 196253/3

13. The method recited in claim 1 wherein: analyzing the generated image-texture measure to perform the biometric function comprises comparing the generated image-texture measure with a reference image-texture measure; the reference image-texture measure was generated from a reference image formed from light scattered from a reference skin site; and the purported skin site is substantially different from the reference skin site.

14. The method recited in claim 1 further comprising: comparing spectral features of the received light with reference spectral features in performing the biometric function.

15. A biometric sensor comprising: a surface adapted for contact with a purported skin site of an individual; an illumination subsystem disposed to illuminate the purported skin site with illumination light having a plurality of wavelengths when the purported skin site is in contact with the surface; a detection subsystem disposed to receive light scattered from the purported skin site, wherein the light is received substantially in a plane that includes the surface; and a computational unit interfaced with the detection subsystem and having: instructions for forming a plurality of images corresponding to different of the plurality of wavelengths from the received light; instructions for generating an image-texture measure from the plurality of images; and instructions for analyzing the generated image-texture measure to perform the biometric function.

16. The biometric sensor recited in claim 15 wherein: the biometric function comprises an antispoofing function; and 38 1 96253/3 the instructions for analyzing the generated image-texture measure comprise instructions for determining whether the purported skin site comprises living tissue from the generated image-texture measure.

17. The biometric sensor recited in claim 15 wherein: the biometric function comprises an identity function; and the instructions for analyzing the generated image-texture measure comprise instructions for determining an identity of the individual from the generated image-texture measure.

18. The biometric sensor recited in claim 15 wherein: the biometric function comprises a demographic or anthropometric function; and the instructions for analyzing the generated image-texture measure comprise instructions for estimating a demographic or anthropometric characteristic of the individual from the generated image-texture measure.

19. The biometric sensor recited in claim 15 further comprising an imaging detector, wherein: the surface is a surface of the imaging detector; and the detection subsystem comprises the imaging detector and is configured to receive light scattered from the purported skin site at the imaging detector.

20. The biometric sensor recited in claim 15 further comprising: an imaging detector disposed outside the plane; and an optical arrangement configured to translate a pattern of light from the plane to the imaging detector without substantial degradation or attenuation of the pattern, wherein the detection subsystem comprises the imaging detector and is configured to receive the translated pattern at the imaging detector.

21. The biometric sensor recited in claim 15 wherein the illumination subsystem is configured to illuminate the purported skin site with white light. 39 196253/3

22. The biometric sensor recited in claim 15 wherein the instructions for generating the image-texture measure comprise instructions for performing a spatial moving-window analysis of each of the plurality of images.

23. The biometric sensor recited in claim 22 wherein the instructions for performing the spatial moving-window analysis comprise instructions for calculating moving-window Fourier transforms on the plurality of images.

24. The biometric sensor recited in claim 22 wherein the instructions for performing the spatial moving-window analysis comprise instructions for calculating a moving-window centrality measure and a moving-window variability measure of the plurality of images.

25. The biometric sensor recited in claim 15 wherein the detection subsystem comprises a monochromatic imaging detector and is configured to the light scattered from the purported skin site at the monochromatic imaging detector.

26. The biometric sensor recited in claim 15 wherein the detection subsystem comprises a color imaging detector and is configured to the light scattered from the purported skin site at the color imaging detector.

27. The biometric sensor recited in claim 15 wherein the instructions for analyzing the generated image-texture measure to perform the biometric function comprise instructions for comparing the generated image-texture measure with a reference image-texture measure; the reference image-texture measure was generated from a reference image formed from light scattered from a reference skin site; and the purported skin site is substantially different from the reference skin site. 40